Mitosis requires mechanisms that mechanically control chromosome movements to ensure equal segregation of chromosomes to daughter cells. Forces that move mitotic chromosomes are generated by microtubule dynamics within the mitotic spindle and by molecular motor proteins. The chromokinesin KIF22 (or Kid, kinesin-like DNA-binding protein) is a plus-end directed member of the kinesin-10 family (Yajima et al., 2003). KIF22 and its orthologs, including Nod (Drosophila melanogaster) (Zhang et al., 1990) and Xkid (Xenopus laevis) (Antonio et al., 2000; Funabiki and Murray, 2000; Takagi et al., 2013), generate forces that move chromosomes away from the spindle poles. Structurally, KIF22 contains a conserved kinesin motor domain responsible for ATP hydrolysis and microtubule binding (Tokai et al., 1996; Yajima et al., 2003), a second microtubule-binding domain in the tail (Shiroguchi et al., 2003), a predicted coiled-coil domain (Shiroguchi et al., 2003), and a C-terminal DNA binding domain, which includes a helix-hairpin-helix motif (Tokai et al., 1996; Figure 1A). Precisely how KIF22’s force generating activity is regulated in mitotic cells and how this regulation contributes to spindle function and cell viability remains incompletely understood.

Figure 1

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In interphase, KIF22 localizes to the nucleus (Levesque and Compton, 2001; Tokai et al., 1996). As cells enter mitosis, chromosomes condense and KIF22 binds along chromosome arms (Levesque and Compton, 2001; Tokai et al., 1996). In prometaphase, chromosomes must congress and align at the center of the spindle. The interactions of the KIF22 motor domain with spindle microtubules and the KIF22 tail with chromosome arms allow the motor to generate polar ejection forces (Bieling et al., 2010; Brouhard and Hunt, 2005), which push the arms of chromosomes away from the spindle poles and toward the center of the spindle (Marshall et al., 2001; Rieder and Salmon, 1994; Rieder et al., 1986), contributing to chromosome congression in prometaphase (Iemura and Tanaka, 2015; Levesque and Compton, 2001; Wandke et al., 2012), as well as chromosome arm orientation (Levesque and Compton, 2001; Wandke et al., 2012). In metaphase, polar ejection forces also contribute to chromosome oscillation and alignment (Antonio et al., 2000; Funabiki and Murray, 2000; Levesque and Compton, 2001; Levesque et al., 2003; Stumpff et al., 2012; Takagi et al., 2013; Tokai-Nishizumi et al., 2005). Purified KIF22 is monomeric (Shiroguchi et al., 2003; Yajima et al., 2003), and the forces generated by KIF22 on chromosomes arms may represent the collective action of many monomers. In anaphase, KIF22 is inactivated to reduce polar ejection forces and allow chromosomes to segregate toward the spindle poles (Soeda et al., 2016; Su et al., 2016; Wolf et al., 2006).

The generation of polar ejection forces by KIF22 is regulated by the activity of cyclin-dependent kinase 1 (CDK1)/cyclin B, which is high in prometa- and metaphase, and drops sharply at the metaphase to anaphase transition when cyclin B is degraded (Hershko, 1999; Morgan, 1995). KIF22 is phosphorylated by CDK1/cyclin B at T463, a residue in the tail of the motor between the second microtubule-binding and coiled-coil domains. Phosphorylation of T463 is required for polar ejection force generation in prometa- and metaphase, and dephosphorylation of T463 is necessary for the suspension of polar ejection forces to allow chromosome segregation in anaphase (Soeda et al., 2016). Although a reduction of polar ejection forces in anaphase is a necessary step for proper anaphase chromosome segregation, it is not clear how this contributes to a shift in force balance within the spindle at the metaphase to anaphase transition. Furthermore, while several regions of the KIF22 tail are known to contribute to KIF22’s inactivation as cells transition to anaphase, how motor activity is downregulated has not been resolved. Phosphoproteomic studies have identified sites of phosphorylation within KIF22’s α2 helix (Kettenbach et al., 2011; Olsen et al., 2010; Rigbolt et al., 2011), suggesting this region, in addition to the tail, may also be important for the regulation of motor activity.

The study of pathogenic mutations can often provide insight into the regulation and function of cellular proteins. Mutations in KIF22 cause the developmental disorder spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type (SEMDJL2, also referred to as Hall Type or lepto-SEMDJL) (Boyden et al., 2011; Min et al., 2011; Tüysüz et al., 2015). Four point mutations in two amino acids have been reported in SEMDJL2 patients (Boyden et al., 2011; Min et al., 2011; Tüysüz et al., 2015; Figure 1A). These mutations occur in adjacent residues P148 and R149 in the α2 helix of the KIF22 motor domain (Figure 1B). P148 and R149 are conserved in kinesin-10 family members across species (Figure 1C) and in many human members of the kinesin superfamily (Figure 1D). However, no pathogenic mutations in the homologous proline or arginine residues have been recorded in OMIM (Online Mendelian Inheritance in Man; https://omim.org/). All identified patients are heterozygous for a single mutation in KIF22. Mutations in KIF22 dominantly cause SEMDJL2, and patients with both de novo and inherited mutations have been identified (Boyden et al., 2011; Min et al., 2011).

Although KIF22 mRNA is expressed throughout the body (Human Protein Atlas; http://www.proteinatlas.org; Uhlén et al., 2015), the effects of these mutations are largely tissue-specific, and the development of the skeletal system is most affected in SEMDJL2 patients. A primary symptom of SEMDJL2 is short stature, resulting from shortening of both the trunk and the limbs. Additionally, patients presented with joint laxity, midface hypoplasia, scoliosis, and leptodactyly, a narrowing of the fingers (Boyden et al., 2011; Min et al., 2011). In very young children with SEMDJL2, the softness of the cartilage in the larynx and trachea caused respiratory issues (Boyden et al., 2011). Growth plate radiology demonstrated delayed maturation of the metaphyses and epiphyses in SEMDJL2 patients, and symptoms became more pronounced as patients aged (Tüysüz et al., 2015). Leptodactyly, specifically, was only observed in older (young adult) patients (Boyden et al., 2011).

Pathogenic mutations in the KIF22 motor domain were predicted to be loss of function mutations (Min et al., 2011). However, KIF22 knockout in mice did not affect skeletal development. Loss of KIF22 was lethal early in embryogenesis for approximately 50% of embryos, but mice that survived past this point developed to adulthood and demonstrated no gross abnormalities or pathologies (Ohsugi et al., 2003). As such, the cellular mechanism by which mutations in KIF22 affect development is unknown.

Here, we characterize an additional patient with a mutation in KIF22 and assess the effect of previously reported and novel pathogenic mutations on the function of KIF22 in mitosis. We demonstrate that mutations are not loss of function mutations, and do not alter the localization of the motor or the generation of polar ejection forces in prometaphase. Instead, mutations disrupt anaphase chromosome segregation, consistent with continued KIF22 activation and consequent polar ejection force generation in anaphase. Defects in anaphase chromosome segregation affect daughter cell nuclear morphology and, in a subset of cells, prevent cytokinesis. These findings demonstrate that anaphase inactivation of KIF22 is critical for daughter cell fitness. As such, mitotic defects may contribute to pathogenesis in patients with KIF22 mutations. Additionally, we demonstrate that aberrant polar ejection force generation in anaphase primarily affects the segregation of chromosomes by limiting chromosome arm movements in anaphase A and spindle pole separation in anaphase B, offering insight into the balance of forces required for accurate chromosome segregation in anaphase. Finally, we demonstrate that mimicking phosphorylation of T158 in the α2 helix disrupts anaphase chromosome segregation, confirming that the region of the motor domain affected by SEMDJL2 mutations also contributes to the mechanism by which KIF22 is inactivated in anaphase.

We have determined that pathogenic mutations in KIF22 disrupt anaphase chromosome segregation, causing chromosome recongression, nuclear morphology defects, reduced proliferation, and, in a subset of cells, cytokinesis failure. Wild-type KIF22 is inactivated in anaphase (Soeda et al., 2016), resulting in an attenuation of polar ejection forces, which allows chromosomes to move toward the spindle poles (Figure 10A). The phenotypes we observe in cells expressing KIF22-GFP with pathogenic mutations are consistent with KIF22 remaining active in anaphase (Figure 10B). Polar ejection forces could cause recongression by continuing to push chromosomes away from the spindle poles during anaphase A and disrupting spindle elongation during anaphase B. These forces result in aberrant positioning of chromosomes during telophase and cytokinesis, which could cause the nuclear morphology defects and cytokinesis failure we observe in cells expressing mutant KIF22-GFP. Consistent with this model, mimicking phosphorylation of T463 to prevent KIF22 inactivation in anaphase phenocopies the effects of pathogenic mutations. Thus, we conclude that pathogenic mutations result in a gain of KIF22 function, which aligns with findings that KIF22 mutations are dominant in heterozygous patients (Boyden et al., 2011; Min et al., 2011; Tüysüz et al., 2015). The effects of pathogenic mutations on chromosome movements in anaphase are consistent with observations of chromosome recongression in cells with altered CDK1 activity (Su et al., 2016; Wolf et al., 2006) or altered tail structure (Soeda et al., 2016). Our work additionally demonstrates the involvement of the motor domain α2 helix in this process and the consequences of recongression on cytokinesis, daughter cell nuclear morphology, and proliferation.

Figure 10

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Mutations in both the motor domain (P148L, P148S, R149L, and R149Q) and the coiled-coil domain (V475G) of KIF22 disrupt chromosome segregation in a manner consistent with a failure of KIF22 inactivation in anaphase. Additionally, mimicking phosphorylation of T158 in the motor domain or T463 in the tail also disrupts chromosome segregation. These findings demonstrate that the motor domain α2 helix participates in the process of KIF22 inactivation, adding to studies that demonstrate that deletion of the tail microtubule-binding domain and deletion or disruption of the coiled-coil domain prevent the inactivation of KIF22 in anaphase (Soeda et al., 2016). Phosphorylation of KIF22 T158 has been detected in mitotic cells, but the relative phosphorylation levels of this residue at different times in mitosis are not known (Olsen et al., 2010). Further studies are needed to determine the time course of T158 phosphorylation, whether this phosphorylation regulates KIF22 function in mitosis, and if T158 and T463 phosphorylation control KIF22 activity independently or via the same mechanism.

The physical mechanism of KIF22 inactivation is unknown, and our results can be interpreted in the context of several models, which are not mutually exclusive. Previous work has proposed that the tail of KIF22 may interact with microtubules to suspend polar ejection force generation, as KIF22 inactivation requires the tail second microtubule-binding and coiled-coil domains (Soeda et al., 2016). Mimicking phosphorylation of T463 disrupts inactivation (Soeda et al., 2016). Dephosphorylation of T463 could facilitate tail-microtubule interaction, or charge change at T463 could disrupt the structure of the microtubule-binding or coiled-coil domains. The interaction between the tail of KIF22 and the microtubule may not be strong or long-lasting, as deletion of the tail microtubule-binding domain does not alter the velocity of KIF22 (Shiroguchi et al., 2003), and KIF22 tail fragments containing the second microtubule-binding domain do not localize to spindle microtubules. In the framework of a tail-microtubule interaction inactivating KIF22, the mutation in the tail (V745G) could disrupt anaphase chromosome segregation by altering this interaction with microtubules. Whether or how the α2 helix could contribute to this mechanism is less clear. The α2 helix faces away from the surface of the microtubule, and we would not predict that mutations in this structure would directly alter the association of the motor domain with the microtubule. It is possible that this region of the motor domain could facilitate or strengthen an interaction between the tail and the microtubule surface indirectly.

Alternatively, given that mutations in the tail and motor domain of KIF22 both disrupt chromosome segregation, the tail and motor domain may interact to inactivate the motor. Head-tail autoinhibition is a known regulatory mechanism of other members of the kinesin superfamily (Blasius et al., 2021; Coy et al., 1999; Espeut et al., 2008; Friedman and Vale, 1999; Hammond et al., 2010; Hammond et al., 2009; Imanishi et al., 2006; Ren et al., 2018; Verhey and Hammond, 2009; Verhey et al., 1998), and disruption of autoinhibition can be a mechanism of disease pathogenesis (Asselin et al., 2020; Bianchi et al., 2016; Blasius et al., 2021; Cheng et al., 2014; Pant et al., 2022; van der Vaart et al., 2013). Mutations in either the tail or motor domain could disrupt this interaction, preventing KIF22 inactivation in anaphase. Dephosphorylation of both T463 in the tail and T158 in the motor domain could facilitate this interaction. Co-IP experiments did not demonstrate an interaction between the motor domain and tail of KIF22 under the conditions of our assays. However, it is possible that a transient head-tail interaction may not be detectable by IP. Thus, further studies are needed to rule out an inactivating interaction between these domains.

Rather than physically interacting with the motor domain, it is also possible that structural changes in the tail of KIF22 could have allosteric effects on the motor domain. An allosteric mechanism by which conformational changes are propagated down the stalk to the motor domain has recently been proposed to contribute to the inactivation of kinesin-1 motors by kinesin light chain, which binds the tail (Chiba et al., 2021). KIF22 inactivation may be caused by altered motor domain mechanochemistry, which changes in the tail could affect allosterically and modification of α2 could affect directly. This could explain the effect of tail and motor domain mutations, as well as the effects of mimicking tail and motor domain phosphorylation, on KIF22 activity.

An additional consideration is that pathogenic mutations may affect the inactivation of KIF22 in anaphase by altering phosphoregulation of KIF22 activity. If mutations prevented the dephosphorylation of T158 and T463 in anaphase this could cause anaphase recongression. However, addition of a phosphonull T463A mutation to KIF22 with coiled-coil or microtubule-binding domain deletions does not rescue anaphase chromosome recongression defects (Soeda et al., 2016), suggesting that the role of the KIF22 tail in motor inactivation is not only to facilitate dephosphorylation of T463. Future studies using structural approaches will be required to distinguish between possible mechanisms of KIF22 inactivation.

The regulation of the motor domain α2 helix in KIF22 inactivation may inform our understanding of additional kinesin motors, as amino acids P148 and R149 are conserved in a number of members of the kinesin superfamily (Figure 1D). Similarly, phosphorylation or acetylation of amino acids in the α2 helix has been reported for members of the kinesin-3 (KIF13A S134) (Dephoure et al., 2008), kinesin-5 (KIF11 Y125, K146) (Bickel et al., 2017; Choudhary et al., 2009), kinesin-6 (KIF20B S182 and KIF23 S125) (Hegemann et al., 2011; Sharma et al., 2014; Shiromizu et al., 2013), and kinesin-14 (KIFC3 S557) (Sharma et al., 2014) families. Phosphorylation of Y125 (Bickel et al., 2017) and acetylation of K146 (Muretta et al., 2018) in KIF11 (Eg5) have been shown to modulate motor activity, and the functions of the remaining reported post-translation modifications in the α2 helix are yet to be characterized. Acetylation of KIF11 at K146 increases the stall force of the motor and slows anaphase spindle pole separation (Muretta et al., 2018). This post-translational modification represents a mechanism by which the activity of KIF11 could be regulated at the metaphase to anaphase transition to generate sliding forces for spindle assembly in prometaphase and control spindle pole separation in anaphase, analogous to how post-translational modifications of KIF22 regulate motor activity to ensure both chromosome congression and alignment in prometaphase and chromosome segregation in anaphase.

While chromosomes in some cells, particularly those expressing KIF22-GFP at high levels, completely failed to segregate and decondensed in the center of the spindle, most cells demonstrated chromosome recongression wherein poleward motion of chromosomes begins, but then chromosomes switch direction and move anti-poleward. These dynamics may be due to differences in microtubule density closer to the poles compared to the center of the spindle. This model is consistent with work demonstrating that in monopolar spindles, poleward movement of chromosomes is limited by chromosomes reaching a threshold density of microtubules at which polar ejection forces are sufficient to cause chromosomes to switch to anti-poleward movement (Cassimeris et al., 1994). We observed that chromosomes on the periphery of the spindle remain closer to the poles while central chromosomes are pushed further away from the poles during recongression in cells expressing KIF22-GFP with pathogenic mutations. This could also be explained by the central chromosomes encountering a higher density of microtubules, and KIF22 bound to these chromosomes therefore generating higher levels of polar ejection forces. In addition, this mechanism is consistent with observations that oscillations of peripheral chromosomes are reduced compared to chromosomes at the center of the spindle (Cameron et al., 2006; Cimini et al., 2004; Civelekoglu-Scholey et al., 2013; Stumpff et al., 2008), which could also be explained by reduced peripheral microtubule density limiting peripheral polar ejection force generation.

Our assessment of the relative trajectories of chromosomes, centromeres, and spindle poles offers insight into the relative magnitudes of polar ejection forces and other anaphase forces. Expression of KIF22-GFP with pathogenic mutations did not alter the distance between centromeres and spindle poles, indicating that while anaphase polar ejection forces altered the position of chromosome arms within the spindle, these forces were not sufficient to prevent the shortening of k-fibers. However, the expression of mutant KIF22-GFP did alter the movements of the spindle poles, allowing assessment of the relative magnitude of polar ejection forces compared to the forces generated by the sliding of antiparallel spindle microtubules to separate the spindle poles in anaphase (Brust-Mascher et al., 2004; Fu et al., 2009; Nislow et al., 1992; Sawin et al., 1992; Straight et al., 1998; Tanenbaum et al., 2009; van Heesbeen et al., 2014; Vukušić et al., 2019; Vukušić et al., 2021). In cells expressing mutant KIF22-GFP, spindle pole separation stalled, and poles moved closer to one another during anaphase chromosome recongression. This suggests that the polar ejection forces collectively generated by mutant KIF22 motors are of greater magnitude than the forces sliding the spindle poles apart during anaphase B. Although it is important to note that this phenotype was observed with moderate overexpression of mutant KIF22, the observed effects on spindle pole separation underscore the importance of KIF22 inactivation, and imply that reducing polar ejection forces is required for both anaphase A and anaphase B. This force balance may differ between cell types, as tail domain deletions that alter chromosome movements do not disrupt anaphase B in mouse oocyte meiosis (Soeda et al., 2016).

Patients with mutations in KIF22 exhibit defects in skeletal development. The pathology observed in the patient heterozygous for the V475G mutation differs from those seen in SEMDJL2 patients with motor domain mutations (Figure 1E and F; Boyden et al., 2011; Min et al., 2011; Tüysüz et al., 2015). However, a meaningful comparison of pathologies between patients is limited both by the fact that only a single patient with a mutation in the tail of KIF22 has been identified, and by the considerable variation in clinical presentation between patients with motor domain mutations, even between patients with the same point mutation (Boyden et al., 2011; Min et al., 2011; Tüysüz et al., 2015). The defects in chromosome segregation we observed in cells expressing mutant KIF22-GFP may contribute to skeletal developmental pathogenesis. Mutations could cause reduced proliferation of growth plate chondrocytes, which in turn could limit bone growth. Disrupting cytokinesis in the growth plate causes shorter bones and stature in mice (Gan et al., 2019), and mutations in KIF22 could affect development via this mechanism. The presence of pathologies in other cartilaginous tissues, including the larynx and trachea, in patients with mutations in the motor domain of KIF22 (Boyden et al., 2011) is also consistent with a disease etiology based in aberrant chondrocyte proliferation. Defects in mitosis could result in tissue-specific patient pathology based on differences in force balance within anaphase spindles in different cell types arising from different expression or activity levels of mitotic force generators or regulators. Growth plate chondrocytes, particularly, are organized into columns and must divide under geometric constraints (Dodds, 1930), which could increase sensitivity to anaphase force imbalances. Additionally, we cannot exclude the possibility that these mutations may affect the function of interphase cells, which could affect development via a mechanism independent from the effects of the mutations on mitosis. Future work will be required to distinguish among these possible explanations.

All data generated or analyzed during this study are included in the manuscript and supporting files. Source Data files have been provided for Figure 2, Figure 2- Figure Supplement 1, Figure 3, Figure 4, Figure 4- Figure Supplement 1, Figure 5, Figure 6, Figure 6- Figure Supplement 1, Figure 7, Figure 8, Figure 8- Figure Supplement 1, Figure 9, Figure 9- Figure Supplement 1, Figure 9- Figure Supplement 2, and Figure 9- Figure Supplement 3.

1. 1. Adzhubei IA
   2. Schmidt S
   3. Peshkin L
   4. Ramensky VE
   5. Gerasimova A
   6. Bork P
   7. Kondrashov AS
   8. Sunyaev SR

   (2010) A method and server for predicting damaging missense mutations

   Nature Methods 7:248–249.

   https://doi.org/10.1038/nmeth0410-248

   • PubMed
   • Google Scholar
2. 1. Antonio C
   2. Ferby I
   3. Wilhelm H
   4. Jones M
   5. Karsenti E
   6. Nebreda AR
   7. Vernos I

   (2000) Xkid, a chromokinesin required for chromosome alignment on the metaphase plate

   Cell 102:425–435.

   https://doi.org/10.1016/s0092-8674(00)00048-9

   • PubMed
   • Google Scholar
3. 1. Asbury CL

   (2017) Anaphase A: disassembling microtubules move chromosomes toward spindle poles

   Biology 6:E15.

   https://doi.org/10.3390/biology6010015

   • PubMed
   • Google Scholar
4. 1. Asselin L
   2. Rivera Alvarez J
   3. Heide S
   4. Bonnet CS
   5. Tilly P
   6. Vitet H
   7. Weber C
   8. Bacino CA
   9. Baranaño K
   10. Chassevent A
   11. Dameron A
   12. Faivre L
   13. Hanchard NA
   14. Mahida S
   15. McWalter K
   16. Mignot C
   17. Nava C
   18. Rastetter A
   19. Streff H
   20. Thauvin-Robinet C
   21. Weiss MM
   22. Zapata G
   23. Zwijnenburg PJG
   24. Saudou F
   25. Depienne C
   26. Golzio C
   27. Héron D
   28. Godin JD

   (2020) Mutations in the KIF21B kinesin gene cause neurodevelopmental disorders through imbalanced canonical motor activity

   Nature Communications 11:1–18.

   https://doi.org/10.1038/s41467-020-16294-6

   • PubMed
   • Google Scholar
5. 1. Bianchi S
   2. van Riel WE
   3. Kraatz SHW
   4. Olieric N
   5. Frey D
   6. Katrukha EA
   7. Jaussi R
   8. Missimer J
   9. Grigoriev I
   10. Olieric V
   11. Benoit RM
   12. Steinmetz MO
   13. Akhmanova A
   14. Kammerer RA

   (2016) Structural basis for misregulation of kinesin KIF21A autoinhibition by CFEOM1 disease mutations

   Scientific Reports 6:30668.

   https://doi.org/10.1038/srep30668

   • PubMed
   • Google Scholar
6. 1. Bickel KG
   2. Mann BJ
   3. Waitzman JS
   4. Poor TA
   5. Rice SE
   6. Wadsworth P

   (2017) Src family kinase phosphorylation of the motor domain of the human kinesin-5, Eg5

   Cytoskeleton 74:317–330.

   https://doi.org/10.1002/cm.21380

   • PubMed
   • Google Scholar
7. 1. Bieling P
   2. Kronja I
   3. Surrey T

   (2010) Microtubule motility on reconstituted meiotic chromatin

   Current Biology 20:763–769.

   https://doi.org/10.1016/j.cub.2010.02.067

   • PubMed
   • Google Scholar
8. 1. Blasius TL
   2. Yue Y
   3. Prasad R
   4. Liu X
   5. Gennerich A
   6. Verhey KJ

   (2021) Sequences in the stalk domain regulate auto-inhibition and ciliary tip localization of the immotile kinesin-4 KIF7

   Journal of Cell Science 134:jcs258464.

   https://doi.org/10.1242/jcs.258464

   • PubMed
   • Google Scholar
9. 1. Bodnar AG
   2. Ouellette M
   3. Frolkis M
   4. Holt SE
   5. Chiu CP
   6. Morin GB
   7. Harley CB
   8. Shay JW
   9. Lichtsteiner S
   10. Wright WE

   (1998) Extension of life-span by introduction of telomerase into normal human cells

   Science 279:349–352.

   https://doi.org/10.1126/science.279.5349.349

   • PubMed
   • Google Scholar
10. 1. Boyden ED
    2. Campos-Xavier AB
    3. Kalamajski S
    4. Cameron TL
    5. Suarez P
    6. Tanackovic G
    7. Tanackovich G
    8. Andria G
    9. Ballhausen D
    10. Briggs MD
    11. Hartley C
    12. Cohn DH
    13. Davidson HR
    14. Hall C
    15. Ikegawa S
    16. Jouk P-S
    17. König R
    18. Megarbané A
    19. Nishimura G
    20. Lachman RS
    21. Mortier G
    22. Rimoin DL
    23. Rogers RC
    24. Rossi M
    25. Sawada H
    26. Scott R
    27. Unger S
    28. Valadares ER
    29. Bateman JF
    30. Warman ML
    31. Superti-Furga A
    32. Bonafé L

    (2011) Recurrent dominant mutations affecting two adjacent residues in the motor domain of the monomeric kinesin KIF22 result in skeletal dysplasia and joint laxity

    American Journal of Human Genetics 89:767–772.

    https://doi.org/10.1016/j.ajhg.2011.10.016

    • PubMed
    • Google Scholar
11. 1. Brouhard GJ
    2. Hunt AJ

    (2005) Microtubule movements on the arms of mitotic chromosomes: polar ejection forces quantified in vitro

    PNAS 102:13903–13908.

    https://doi.org/10.1073/pnas.0506017102

    • PubMed
    • Google Scholar
12. 1. Brust-Mascher I
    2. Civelekoglu-Scholey G
    3. Kwon M
    4. Mogilner A
    5. Scholey JM

    (2004) Model for anaphase B: role of three mitotic motors in a switch from poleward flux to spindle elongation

    PNAS 101:15938–15943.

    https://doi.org/10.1073/pnas.0407044101

    • PubMed
    • Google Scholar
13. 1. Cameron LA
    2. Yang G
    3. Cimini D
    4. Canman JC
    5. Kisurina-Evgenieva O
    6. Khodjakov A
    7. Danuser G
    8. Salmon ED

    (2006) Kinesin 5-independent poleward flux of kinetochore microtubules in PtK1 cells

    The Journal of Cell Biology 173:173–179.

    https://doi.org/10.1083/jcb.200601075

    • PubMed
    • Google Scholar
14. 1. Cassimeris L
    2. Rieder CL
    3. Salmon ED

    (1994) Microtubule assembly and kinetochore directional instability in vertebrate monopolar spindles: implications for the mechanism of chromosome congression

    Journal of Cell Science 107 (Pt 1):285–297.

    https://doi.org/10.1242/jcs.107.1.285

    • PubMed
    • Google Scholar
15. 1. Cheng L
    2. Desai J
    3. Miranda CJ
    4. Duncan JS
    5. Qiu W
    6. Nugent AA
    7. Kolpak AL
    8. Wu CC
    9. Drokhlyansky E
    10. Delisle MM
    11. Chan W-M
    12. Wei Y
    13. Propst F
    14. Reck-Peterson SL
    15. Fritzsch B
    16. Engle EC

    (2014) Human CFEOM1 mutations attenuate KIF21A autoinhibition and cause oculomotor axon stalling

    Neuron 82:334–349.

    https://doi.org/10.1016/j.neuron.2014.02.038

    • PubMed
    • Google Scholar
16. Preprint

    1. Chiba K
    2. Ori-McKenney KM
    3. Niwa S
    4. McKenney RJ

    (2021) Reconstitution of Kinesin-1 Activation

    bioRxiv.

    https://doi.org/10.1101/2021.03.12.434960

    • Google Scholar
17. 1. Choudhary C
    2. Kumar C
    3. Gnad F
    4. Nielsen ML
    5. Rehman M
    6. Walther TC
    7. Olsen JV
    8. Mann M

    (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions

    Science 325:834–840.

    https://doi.org/10.1126/science.1175371

    • PubMed
    • Google Scholar
18. 1. Cimini D
    2. Cameron LA
    3. Salmon ED

    (2004) Anaphase spindle mechanics prevent mis-segregation of merotelically oriented chromosomes

    Current Biology 14:2149–2155.

    https://doi.org/10.1016/j.cub.2004.11.029

    • PubMed
    • Google Scholar
19. 1. Civelekoglu-Scholey G
    2. He B
    3. Shen M
    4. Wan X
    5. Roscioli E
    6. Bowden B
    7. Cimini D

    (2013) Dynamic bonds and polar ejection force distribution explain kinetochore oscillations in PtK1 cells

    The Journal of Cell Biology 201:577–593.

    https://doi.org/10.1083/jcb.201301022

    • PubMed
    • Google Scholar
20. 1. Cousin MA
    2. Conboy E
    3. Wang JS
    4. Lenz D
    5. Schwab TL
    6. Williams M
    7. Abraham RS
    8. Barnett S
    9. El-Youssef M
    10. Graham RP
    11. Gutierrez Sanchez LH
    12. Hasadsri L
    13. Hoffmann GF
    14. Hull NC
    15. Kopajtich R
    16. Kovacs-Nagy R
    17. Li JQ
    18. Marx-Berger D
    19. McLin V
    20. McNiven MA
    21. Mounajjed T
    22. Prokisch H
    23. Rymen D
    24. Schulze RJ
    25. Staufner C
    26. Yang Y
    27. Clark KJ
    28. Lanpher BC
    29. Klee EW

    (2019) RINT1 Bi-allelic variations cause infantile-onset recurrent acute liver failure and skeletal abnormalities

    American Journal of Human Genetics 105:108–121.

    https://doi.org/10.1016/j.ajhg.2019.05.011

    • PubMed
    • Google Scholar
21. 1. Coy DL
    2. Hancock WO
    3. Wagenbach M
    4. Howard J

    (1999) Kinesin’s tail domain is an inhibitory regulator of the motor domain

    Nature Cell Biology 1:288–292.

    https://doi.org/10.1038/13001

    • PubMed
    • Google Scholar
22. 1. Dephoure N
    2. Zhou C
    3. Villén J
    4. Beausoleil SA
    5. Bakalarski CE
    6. Elledge SJ
    7. Gygi SP

    (2008) A quantitative atlas of mitotic phosphorylation

    PNAS 105:10762–10767.

    https://doi.org/10.1073/pnas.0805139105

    • PubMed
    • Google Scholar
23. 1. Dodds GS

    (1930) Row formation and other types of arrangement of cartilage cells in endochondral ossification

    The Anatomical Record 46:385–399.

    https://doi.org/10.1002/ar.1090460409

    • Google Scholar
24. 1. Espeut J
    2. Gaussen A
    3. Bieling P
    4. Morin V
    5. Prieto S
    6. Fesquet D
    7. Surrey T
    8. Abrieu A

    (2008) Phosphorylation relieves autoinhibition of the kinetochore motor Cenp-E

    Molecular Cell 29:637–643.

    https://doi.org/10.1016/j.molcel.2008.01.004

    • PubMed
    • Google Scholar
25. 1. Friedman DS
    2. Vale RD

    (1999) Single-molecule analysis of kinesin motility reveals regulation by the cargo-binding tail domain

    Nature Cell Biology 1:293–297.

    https://doi.org/10.1038/13008

    • PubMed
    • Google Scholar
26. 1. Fu C
    2. Ward JJ
    3. Loiodice I
    4. Velve-Casquillas G
    5. Nedelec FJ
    6. Tran PT

    (2009) Phospho-regulated interaction between kinesin-6 Klp9p and microtubule bundler Ase1p promotes spindle elongation

    Developmental Cell 17:257–267.

    https://doi.org/10.1016/j.devcel.2009.06.012

    • PubMed
    • Google Scholar
27. 1. Funabiki H
    2. Murray AW

    (2000) The Xenopus chromokinesin Xkid is essential for metaphase chromosome alignment and must be degraded to allow anaphase chromosome movement

    Cell 102:411–424.

    https://doi.org/10.1016/s0092-8674(00)00047-7

    • PubMed
    • Google Scholar
28. 1. Gan H
    2. Xue W
    3. Gao Y
    4. Zhu G
    5. Chan D
    6. Cheah KSE
    7. Huang J

    (2019) KIF5B modulates central spindle organization in late-stage cytokinesis in chondrocytes

    Cell & Bioscience 9:85.

    https://doi.org/10.1186/s13578-019-0344-5

    • PubMed
    • Google Scholar
29. 1. Gillingham AK
    2. Munro S

    (2000) The PACT domain, a conserved centrosomal targeting motif in the coiled-coil proteins AKAP450 and pericentrin

    EMBO Reports 1:524–529.

    https://doi.org/10.1093/embo-reports/kvd105

    • PubMed
    • Google Scholar
30. 1. Haila S
    2. Hästbacka J
    3. Böhling T
    4. Karjalainen-Lindsberg ML
    5. Kere J
    6. Saarialho-Kere U

    (2001) SLC26A2 (diastrophic dysplasia sulfate transporter) is expressed in developing and mature cartilage but also in other tissues and cell types

    The Journal of Histochemistry and Cytochemistry 49:973–982.

    https://doi.org/10.1177/002215540104900805

    • PubMed
    • Google Scholar
31. 1. Hammond JW
    2. Cai D
    3. Blasius TL
    4. Li Z
    5. Jiang Y
    6. Jih GT
    7. Meyhofer E
    8. Verhey KJ

    (2009) Mammalian Kinesin-3 motors are dimeric in vivo and move by processive motility upon release of autoinhibition

    PLOS Biology 7:e72.

    https://doi.org/10.1371/journal.pbio.1000072

    • PubMed
    • Google Scholar
32. 1. Hammond JW
    2. Blasius TL
    3. Soppina V
    4. Cai D
    5. Verhey KJ

    (2010) Autoinhibition of the kinesin-2 motor KIF17 via dual intramolecular mechanisms

    The Journal of Cell Biology 189:1013–1025.

    https://doi.org/10.1083/jcb.201001057

    • PubMed
    • Google Scholar
33. 1. Hatch EM
    2. Fischer AH
    3. Deerinck TJ
    4. Hetzer MW

    (2013) Catastrophic nuclear envelope collapse in cancer cell micronuclei

    Cell 154:47–60.

    https://doi.org/10.1016/j.cell.2013.06.007

    • PubMed
    • Google Scholar
34. 1. Hegemann B
    2. Hutchins JRA
    3. Hudecz O
    4. Novatchkova M
    5. Rameseder J
    6. Sykora MM
    7. Liu S
    8. Mazanek M
    9. Lénárt P
    10. Hériché JK
    11. Poser I
    12. Kraut N
    13. Hyman AA
    14. Yaffe MB
    15. Mechtler K
    16. Peters JM

    (2011) Systematic phosphorylation analysis of human mitotic protein complexes

    Science Signaling 4:rs12.

    https://doi.org/10.1126/scisignal.2001993

    • PubMed
    • Google Scholar
35. 1. Hershko A

    (1999) Mechanisms and regulation of the degradation of cyclin B

    Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 354:1571–1575.

    https://doi.org/10.1098/rstb.1999.0500

    • PubMed
    • Google Scholar
36. 1. Iemura K
    2. Tanaka K

    (2015) Chromokinesin Kid and kinetochore kinesin CENP-E differentially support chromosome congression without end-on attachment to microtubules

    Nature Communications 6:1–11.

    https://doi.org/10.1038/ncomms7447

    • PubMed
    • Google Scholar
37. 1. Imanishi M
    2. Endres NF
    3. Gennerich A
    4. Vale RD

    (2006) Autoinhibition regulates the motility of the C. elegans intraflagellar transport motor OSM-3

    The Journal of Cell Biology 174:931–937.

    https://doi.org/10.1083/jcb.200605179

    • PubMed
    • Google Scholar
38. 1. Ioannidis NM
    2. Rothstein JH
    3. Pejaver V
    4. Middha S
    5. McDonnell SK
    6. Baheti S
    7. Musolf A
    8. Li Q
    9. Holzinger E
    10. Karyadi D
    11. Cannon-Albright LA
    12. Teerlink CC
    13. Stanford JL
    14. Isaacs WB
    15. Xu J
    16. Cooney KA
    17. Lange EM
    18. Schleutker J
    19. Carpten JD
    20. Powell IJ
    21. Cussenot O
    22. Cancel-Tassin G
    23. Giles GG
    24. MacInnis RJ
    25. Maier C
    26. Hsieh CL
    27. Wiklund F
    28. Catalona WJ
    29. Foulkes WD
    30. Mandal D
    31. Eeles RA
    32. Kote-Jarai Z
    33. Bustamante CD
    34. Schaid DJ
    35. Hastie T
    36. Ostrander EA
    37. Bailey-Wilson JE
    38. Radivojac P
    39. Thibodeau SN
    40. Whittemore AS
    41. Sieh W

    (2016) REVEL: an ensemble method for predicting the pathogenicity of rare missense variants

    American Journal of Human Genetics 99:877–885.

    https://doi.org/10.1016/j.ajhg.2016.08.016

    • PubMed
    • Google Scholar
39. 1. Kettenbach AN
    2. Schweppe DK
    3. Faherty BK
    4. Pechenick D
    5. Pletnev AA
    6. Gerber SA

    (2011) Quantitative phosphoproteomics identifies substrates and functional modules of Aurora and Polo-like kinase activities in mitotic cells

    Science Signaling 4:rs5.

    https://doi.org/10.1126/scisignal.2001497

    • PubMed
    • Google Scholar
40. 1. Khandelia P
    2. Yap K
    3. Makeyev EV

    (2011) Streamlined platform for short hairpin RNA interference and transgenesis in cultured mammalian cells

    PNAS 108:12799–12804.

    https://doi.org/10.1073/pnas.1103532108

    • PubMed
    • Google Scholar
41. 1. Lefeber DJ
    2. Morava E
    3. Jaeken J

    (2011) How to find and diagnose a CDG due to defective N-glycosylation

    Journal of Inherited Metabolic Disease 34:849–852.

    https://doi.org/10.1007/s10545-011-9370-0

    • PubMed
    • Google Scholar
42. 1. Levesque AA
    2. Compton DA

    (2001) The chromokinesin Kid is necessary for chromosome arm orientation and oscillation, but not congression, on mitotic spindles

    The Journal of Cell Biology 154:1135–1146.

    https://doi.org/10.1083/jcb.200106093

    • PubMed
    • Google Scholar
43. 1. Levesque AA
    2. Howard L
    3. Gordon MB
    4. Compton DA

    (2003) A functional relationship between NuMA and kid is involved in both spindle organization and chromosome alignment in vertebrate cells

    Molecular Biology of the Cell 14:3541–3552.

    https://doi.org/10.1091/mbc.e03-02-0082

    • PubMed
    • Google Scholar
44. 1. Liu D
    2. Vleugel M
    3. Backer CB
    4. Hori T
    5. Fukagawa T
    6. Cheeseman IM
    7. Lampson MA

    (2010) Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase

    The Journal of Cell Biology 188:809–820.

    https://doi.org/10.1083/jcb.201001006

    • PubMed
    • Google Scholar
45. Preprint

    1. Liu Y
    2. Mi Y
    3. Mueller T
    4. Kreibich S
    5. Williams EG
    6. Van Drogen A
    7. Borel C
    8. Germain PL
    9. Frank M
    10. Bludau I
    11. Mehnert M
    12. Seifert M
    13. Emmenlauer M
    14. Sorg I
    15. Bezrukov F
    16. Sloan Bena F
    17. Zhou H
    18. Dehio C
    19. Testa G
    20. Saez-Rodriguez J
    21. Antonarakis SE
    22. Hardt WD
    23. Aebersold R

    (2018) Genomic, Proteomic and Phenotypic Heterogeneity in HeLa Cells across Laboratories: Implications for Reproducibility of Research Results

    bioRxiv.

    https://doi.org/10.1101/307421

    • Google Scholar
46. 1. Marquis C
    2. Fonseca CL
    3. Queen KA
    4. Wood L
    5. Vandal SE
    6. Malaby HLH
    7. Clayton JE
    8. Stumpff J

    (2021) Chromosomally unstable tumor cells specifically require KIF18A for proliferation

    Nature Communications 12:1–14.

    https://doi.org/10.1038/s41467-021-21447-2

    • PubMed
    • Google Scholar
47. 1. Marshall WF
    2. Marko JF
    3. Agard DA
    4. Sedat JW

    (2001) Chromosome elasticity and mitotic polar ejection force measured in living Drosophila embryos by four-dimensional microscopy-based motion analysis

    Current Biology 11:569–578.

    https://doi.org/10.1016/S0960-9822(01)00180-4

    • PubMed
    • Google Scholar
48. 1. Min BJ
    2. Kim N
    3. Chung T
    4. Kim OH
    5. Nishimura G
    6. Chung CY
    7. Song HR
    8. Kim HW
    9. Lee HR
    10. Kim J
    11. Kang TH
    12. Seo ME
    13. Yang SD
    14. Kim DH
    15. Lee SB
    16. Kim JI
    17. Seo JS
    18. Choi JY
    19. Kang D
    20. Kim D
    21. Park WY
    22. Cho TJ

    (2011) Whole-exome sequencing identifies mutations of KIF22 in spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type

    The American Journal of Human Genetics 89:760–766.

    https://doi.org/10.1016/j.ajhg.2011.10.015

    • PubMed
    • Google Scholar
49. 1. Morgan DO

    (1995) Principles of CDK regulation

    Nature 374:131–134.

    https://doi.org/10.1038/374131a0

    • PubMed
    • Google Scholar
50. 1. Muretta JM
    2. Reddy BJN
    3. Scarabelli G
    4. Thompson AF
    5. Jariwala S
    6. Major J
    7. Venere M
    8. Rich JN
    9. Willard B
    10. Thomas DD
    11. Stumpff J
    12. Grant BJ
    13. Gross SP
    14. Rosenfeld SS

    (2018) A posttranslational modification of the mitotic kinesin Eg5 that enhances its mechanochemical coupling and alters its mitotic function

    PNAS 115:201718290.

    https://doi.org/10.1073/pnas.1718290115

    • PubMed
    • Google Scholar
51. 1. Nislow C
    2. Lombillo VA
    3. Kuriyama R
    4. McIntosh JR

    (1992) A plus-end-directed motor enzyme that moves antiparallel microtubules in vitro localizes to the interzone of mitotic spindles

    Nature 359:543–547.

    https://doi.org/10.1038/359543a0

    • PubMed
    • Google Scholar
52. 1. Ohsugi M
    2. Tokai-Nishizumi N
    3. Shiroguchi K
    4. Toyoshima YY
    5. Inoue JI
    6. Yamamoto T

    (2003) Cdc2-mediated phosphorylation of Kid controls its distribution to spindle and chromosomes

    The EMBO Journal 22:2091–2103.

    https://doi.org/10.1093/emboj/cdg208

    • PubMed
    • Google Scholar
53. 1. Ohsugi M
    2. Adachi K
    3. Horai R
    4. Kakuta S
    5. Sudo K
    6. Kotaki H
    7. Tokai-Nishizumi N
    8. Sagara H
    9. Iwakura Y
    10. Yamamoto T

    (2008) Kid-mediated chromosome compaction ensures proper nuclear envelope formation

    Cell 132:771–782.

    https://doi.org/10.1016/j.cell.2008.01.029

    • PubMed
    • Google Scholar
54. 1. Olsen JV
    2. Vermeulen M
    3. Santamaria A
    4. Kumar C
    5. Miller ML
    6. Jensen LJ
    7. Gnad F
    8. Cox J
    9. Jensen TS
    10. Nigg EA
    11. Brunak S
    12. Mann M

    (2010) Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis

    Science Signaling 3:ra3.

    https://doi.org/10.1126/scisignal.2000475

    • PubMed
    • Google Scholar
55. Preprint

    1. Pant DC
    2. Parameswaran J
    3. Rao L
    4. Shi L
    5. Chilukuri G
    6. McEachin ZT
    7. Glass J
    8. Bassell GJ
    9. Gennerich A
    10. Jiang J

    (2022) ALS-Linked KIF5A ΔExon27 Mutant Causes Neuronal Toxicity through Gain of Function

    bioRxiv.

    https://doi.org/10.1101/2022.03.05.483071

    • Google Scholar
56. 1. Pena MM
    2. Teper D
    3. Ferreira H
    4. Wang N
    5. Sato KU
    6. Ferro MIT
    7. Ferro JA

    (2020) mCherry fusions enable the subcellular localization of periplasmic and cytoplasmic proteins in Xanthomonas sp

    PLOS ONE 15:e0236185.

    https://doi.org/10.1371/journal.pone.0236185

    • PubMed
    • Google Scholar
57. 1. Quang D
    2. Chen Y
    3. Xie X

    (2015) DANN: a deep learning approach for annotating the pathogenicity of genetic variants

    Bioinformatics 31:761–763.

    https://doi.org/10.1093/bioinformatics/btu703

    • PubMed
    • Google Scholar
58. 1. Ren J
    2. Wang S
    3. Chen H
    4. Wang W
    5. Huo L
    6. Feng W

    (2018) Coiled-coil 1-mediated fastening of the neck and motor domains for kinesin-3 autoinhibition

    PNAS 115:E11933–E11942.

    https://doi.org/10.1073/pnas.1811209115

    • PubMed
    • Google Scholar
59. 1. Rentzsch P
    2. Witten D
    3. Cooper GM
    4. Shendure J
    5. Kircher M

    (2019) CADD: predicting the deleteriousness of variants throughout the human genome

    Nucleic Acids Research 47:D886–D894.

    https://doi.org/10.1093/nar/gky1016

    • PubMed
    • Google Scholar
60. 1. Rieder CL
    2. Davison EA
    3. Jensen LC
    4. Cassimeris L
    5. Salmon ED

    (1986) Oscillatory movements of monooriented chromosomes and their position relative to the spindle pole result from the ejection properties of the aster and half-spindle

    The Journal of Cell Biology 103:581–591.

    https://doi.org/10.1083/jcb.103.2.581

    • PubMed
    • Google Scholar
61. 1. Rieder CL
    2. Salmon ED

    (1994) Motile kinetochores and polar ejection forces dictate chromosome position on the vertebrate mitotic spindle

    The Journal of Cell Biology 124:223–233.

    https://doi.org/10.1083/jcb.124.3.223

    • PubMed
    • Google Scholar
62. 1. Rigbolt KTG
    2. Prokhorova TA
    3. Akimov V
    4. Henningsen J
    5. Johansen PT
    6. Kratchmarova I
    7. Kassem M
    8. Mann M
    9. Olsen JV
    10. Blagoev B

    (2011) System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation

    Science Signaling 4:rs3.

    https://doi.org/10.1126/scisignal.2001570

    • PubMed
    • Google Scholar
63. 1. Ris H

    (1949)

    The anaphase movement of chromosomes in the spermatocytes of the grasshopper

    The Biological Bulletin 96:90–106.

    • PubMed
    • Google Scholar
64. 1. Rossi A
    2. Superti-Furga A

    (2001) Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene (SLC26A2): 22 novel mutations, mutation review, associated skeletal phenotypes, and diagnostic relevance

    Human Mutation 17:159–171.

    https://doi.org/10.1002/humu.1

    • PubMed
    • Google Scholar
65. 1. Samwer M
    2. Schneider MWG
    3. Hoefler R
    4. Schmalhorst PS
    5. Jude JG
    6. Zuber J
    7. Gerlich DW

    (2017) DNA cross-bridging shapes a single nucleus from a set of mitotic chromosomes

    Cell 170:956–972.

    https://doi.org/10.1016/j.cell.2017.07.038

    • PubMed
    • Google Scholar
66. 1. Sawin KE
    2. LeGuellec K
    3. Philippe M
    4. Mitchison TJ

    (1992) Mitotic spindle organization by a plus-end-directed microtubule motor

    Nature 359:540–543.

    https://doi.org/10.1038/359540a0

    • PubMed
    • Google Scholar
67. 1. Schindelin J
    2. Arganda-Carreras I
    3. Frise E
    4. Kaynig V
    5. Longair M
    6. Pietzsch T
    7. Preibisch S
    8. Rueden C
    9. Saalfeld S
    10. Schmid B
    11. Tinevez J-Y
    12. White DJ
    13. Hartenstein V
    14. Eliceiri K
    15. Tomancak P
    16. Cardona A

    (2012) Fiji: an open-source platform for biological-image analysis

    Nature Methods 9:676–682.

    https://doi.org/10.1038/nmeth.2019

    • PubMed
    • Google Scholar
68. 1. Schneider CA
    2. Rasband WS
    3. Eliceiri KW

    (2012) NIH Image to ImageJ: 25 years of image analysis

    Nature Methods 9:671–675.

    https://doi.org/10.1038/nmeth.2089

    • PubMed
    • Google Scholar
69. 1. Schwarz JM
    2. Rödelsperger C
    3. Schuelke M
    4. Seelow D

    (2010) MutationTaster evaluates disease-causing potential of sequence alterations

    Nature Methods 7:575–576.

    https://doi.org/10.1038/nmeth0810-575

    • PubMed
    • Google Scholar
70. 1. Serra-Marques A
    2. Houtekamer R
    3. Hintzen D
    4. Canty JT
    5. Yildiz A
    6. Dumont S

    (2020) The mitotic protein NuMA plays a spindle-independent role in nuclear formation and mechanics

    The Journal of Cell Biology 219:348.

    https://doi.org/10.1083/jcb.202004202

    • PubMed
    • Google Scholar
71. 1. Sharma K
    2. D’Souza RCJ
    3. Tyanova S
    4. Schaab C
    5. Wiśniewski JR
    6. Cox J
    7. Mann M

    (2014) Ultradeep human phosphoproteome reveals a distinct regulatory nature of Tyr and Ser/Thr-based signaling

    Cell Reports 8:1583–1594.

    https://doi.org/10.1016/j.celrep.2014.07.036

    • PubMed
    • Google Scholar
72. 1. Shiroguchi K
    2. Ohsugi M
    3. Edamatsu M
    4. Yamamoto T
    5. Toyoshima YY

    (2003) The second microtubule-binding site of monomeric kid enhances the microtubule affinity

    Journal of Biological Chemistry 278:22460–22465.

    https://doi.org/10.1074/jbc.M212274200

    • PubMed
    • Google Scholar
73. 1. Shiromizu T
    2. Adachi J
    3. Watanabe S
    4. Murakami T
    5. Kuga T
    6. Muraoka S
    7. Tomonaga T

    (2013) Identification of missing proteins in the neXtProt database and unregistered phosphopeptides in the phosphoSitePlus database as part of the chromosome-centric human proteome project

    Journal of Proteome Research 12:2414–2421.

    https://doi.org/10.1021/pr300825v

    • PubMed
    • Google Scholar
74. 1. Soeda S
    2. Yamada-Nomoto K
    3. Ohsugi M

    (2016) The microtubule-binding and coiled-coil domains of Kid are required for turning off the polar ejection force at anaphase

    Journal of Cell Science 1:3609–3619.

    https://doi.org/10.1242/jcs.189969

    • PubMed
    • Google Scholar
75. 1. Straight AF
    2. Sedat JW
    3. Murray AW

    (1998) Time-lapse microscopy reveals unique roles for kinesins during anaphase in budding yeast

    Journal of Cell Biology 143:687–694.

    https://doi.org/10.1083/jcb.143.3.687

    • PubMed
    • Google Scholar
76. 1. Stumpff J
    2. von Dassow G
    3. Wagenbach M
    4. Asbury C
    5. Wordeman L

    (2008) The kinesin-8 motor Kif18A suppresses kinetochore movements to control mitotic chromosome alignment

    Developmental Cell 14:252–262.

    https://doi.org/10.1016/j.devcel.2007.11.014

    • PubMed
    • Google Scholar
77. 1. Stumpff J
    2. Wagenbach M
    3. Franck A
    4. Asbury CL
    5. Wordeman L

    (2012) Kif18A and chromokinesins confine centromere movements via microtubule growth suppression and spatial control of kinetochore tension

    Developmental Cell 22:1017–1029.

    https://doi.org/10.1016/j.devcel.2012.02.013

    • PubMed
    • Google Scholar
78. Software

    1. Stumpff J

    (2021) Image-Analysis, version c48d4f7

    Github.

    https://github.com/StumpffLab/Image-Analysis
79. 1. Sturgill EG
    2. Norris SR
    3. Guo Y
    4. Ohi R

    (2016) Kinesin-5 inhibitor resistance is driven by kinesin-12

    The Journal of Cell Biology 213:213–227.

    https://doi.org/10.1083/jcb.201507036

    • PubMed
    • Google Scholar
80. 1. Su KC
    2. Barry Z
    3. Schweizer N
    4. Maiato H
    5. Bathe M
    6. Cheeseman IM

    (2016) A regulatory switch alters chromosome motions at the metaphase-to-anaphase transition

    Cell Reports 17:1728–1738.

    https://doi.org/10.1016/j.celrep.2016.10.046

    • PubMed
    • Google Scholar
81. 1. Tahara K
    2. Takagi M
    3. Ohsugi M
    4. Sone T
    5. Nishiumi F
    6. Maeshima K
    7. Horiuchi Y
    8. Tokai-Nishizumi N
    9. Imamoto F
    10. Yamamoto T
    11. Kose S
    12. Imamoto N

    (2008) Importin-beta and the small guanosine triphosphatase Ran mediate chromosome loading of the human chromokinesin Kid

    The Journal of Cell Biology 180:493–506.

    https://doi.org/10.1083/jcb.200708003

    • PubMed
    • Google Scholar
82. 1. Takagi J
    2. Itabashi T
    3. Suzuki K
    4. Ishiwata S

    (2013) Chromosome position at the spindle equator is regulated by chromokinesin and a bipolar microtubule array

    Scientific Reports 3:746–747.

    https://doi.org/10.1038/srep02808

    • PubMed
    • Google Scholar
83. 1. Tanenbaum ME
    2. Macůrek L
    3. Janssen A
    4. Geers EF
    5. Alvarez-Fernández M
    6. Medema RH

    (2009) Kif15 cooperates with eg5 to promote bipolar spindle assembly

    Current Biology 19:1703–1711.

    https://doi.org/10.1016/j.cub.2009.08.027

    • PubMed
    • Google Scholar
84. 1. Thompson AF
    2. Vandal S
    3. Stumpff J

    (2022) Quantifying changes in chromosome position to assess chromokinesin activity

    Methods in Molecular Biology 2415:139–149.

    https://doi.org/10.1007/978-1-0716-1904-9_10

    • PubMed
    • Google Scholar
85. 1. Tokai N
    2. Fujimoto-Nishiyama A
    3. Toyoshima Y
    4. Yonemura S
    5. Tsukita S
    6. Inoue J
    7. Yamamota T

    (1996) Kid, a novel kinesin-like DNA binding protein, is localized to chromosomes and the mitotic spindle

    The EMBO Journal 15:457–467.

    https://doi.org/10.1002/j.1460-2075.1996.tb00378.x

    • PubMed
    • Google Scholar
86. 1. Tokai-Nishizumi N
    2. Ohsugi M
    3. Suzuki E
    4. Yamamoto T

    (2005) The chromokinesin Kid is required for maintenance of proper metaphase spindle size

    Molecular Biology of the Cell 16:5455–5463.

    https://doi.org/10.1091/mbc.e05-03-0244

    • PubMed
    • Google Scholar
87. 1. Tüysüz B
    2. Yılmaz S
    3. Erener-Ercan T
    4. Bilguvar K
    5. Günel M

    (2015) Spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type: longitudinal observation of radiographic findings in a child heterozygous for a KIF22 mutation

    Pediatric Radiology 45:771–776.

    https://doi.org/10.1007/s00247-014-3159-x

    • PubMed
    • Google Scholar
88. 1. Uhlén M
    2. Fagerberg L
    3. Hallström BM
    4. Lindskog C
    5. Oksvold P
    6. Mardinoglu A
    7. Sivertsson Å
    8. Kampf C
    9. Sjöstedt E
    10. Asplund A
    11. Olsson I
    12. Edlund K
    13. Lundberg E
    14. Navani S
    15. Szigyarto CAK
    16. Odeberg J
    17. Djureinovic D
    18. Takanen JO
    19. Hober S
    20. Alm T
    21. Edqvist PH
    22. Berling H
    23. Tegel H
    24. Mulder J
    25. Rockberg J
    26. Nilsson P
    27. Schwenk JM
    28. Hamsten M
    29. von Feilitzen K
    30. Forsberg M
    31. Persson L
    32. Johansson F
    33. Zwahlen M
    34. von Heijne G
    35. Nielsen J
    36. Pontén F

    (2015) Proteomics. Tissue-based map of the human proteome

    Science 347:1260419.

    https://doi.org/10.1126/science.1260419

    • PubMed
    • Google Scholar
89. 1. van der Vaart B
    2. van Riel WE
    3. Doodhi H
    4. Kevenaar JT
    5. Katrukha EA
    6. Gumy L
    7. Bouchet BP
    8. Grigoriev I
    9. Spangler SA
    10. Yu KL
    11. Wulf PS
    12. Wu J
    13. Lansbergen G
    14. van Battum EY
    15. Pasterkamp RJ
    16. Mimori-Kiyosue Y
    17. Demmers J
    18. Olieric N
    19. Maly IV
    20. Hoogenraad CC
    21. Akhmanova A

    (2013) CFEOM1-associated kinesin KIF21A is a cortical microtubule growth inhibitor

    Developmental Cell 27:145–160.

    https://doi.org/10.1016/j.devcel.2013.09.010

    • PubMed
    • Google Scholar
90. 1. van Heesbeen RGHP
    2. Tanenbaum ME
    3. Medema RH

    (2014) Balanced activity of three mitotic motors is required for bipolar spindle assembly and chromosome segregation

    Cell Reports 8:948–956.

    https://doi.org/10.1016/j.celrep.2014.07.015

    • PubMed
    • Google Scholar
91. 1. Vaser R
    2. Adusumalli S
    3. Leng SN
    4. Sikic M
    5. Ng PC

    (2016) SIFT missense predictions for genomes

    Nature Protocols 11:1–9.

    https://doi.org/10.1038/nprot.2015.123

    • PubMed
    • Google Scholar
92. 1. Verhey KJ
    2. Lizotte DL
    3. Abramson T
    4. Barenboim L
    5. Schnapp BJ
    6. Rapoport TA

    (1998) Light chain– dependent regulation of kinesin’s interaction with microtubules

    Journal of Cell Biology 143:1053–1066.

    https://doi.org/10.1083/jcb.143.4.1053

    • PubMed
    • Google Scholar
93. 1. Verhey KJ
    2. Hammond JW

    (2009) Traffic control: regulation of kinesin motors

    Nature Reviews Molecular Cell Biology 10:765–777.

    https://doi.org/10.1038/nrm2782

    • PubMed
    • Google Scholar
94. 1. Vukušić K
    2. Buđa R
    3. Tolić IM

    (2019) Force-generating mechanisms of anaphase in human cells

    Journal of Cell Science 132:jcs231985.

    https://doi.org/10.1242/jcs.231985

    • PubMed
    • Google Scholar
95. 1. Vukušić K
    2. Ponjavić I
    3. Buđa R
    4. Risteski P
    5. Tolić IM

    (2021) Microtubule-sliding modules based on kinesins EG5 and PRC1-dependent KIF4A drive human spindle elongation

    Developmental Cell 56:1253–1267.

    https://doi.org/10.1016/j.devcel.2021.04.005

    • PubMed
    • Google Scholar
96. 1. Wandke C
    2. Barisic M
    3. Sigl R
    4. Rauch V
    5. Wolf F
    6. Amaro AC
    7. Tan CH
    8. Pereira AJ
    9. Kutay U
    10. Maiato H
    11. Meraldi P
    12. Geley S

    (2012) Human chromokinesins promote chromosome congression and spindle microtubule dynamics during mitosis

    Journal of Cell Biology 198:847–863.

    https://doi.org/10.1083/jcb.201110060

    • PubMed
    • Google Scholar
97. 1. Wolf F
    2. Wandke C
    3. Isenberg N
    4. Geley S

    (2006) Dose-dependent effects of stable cyclin B1 on progression through mitosis in human cells

    The EMBO Journal 25:2802–2813.

    https://doi.org/10.1038/sj.emboj.7601163

    • PubMed
    • Google Scholar
98. 1. Yajima J
    2. Edamatsu M
    3. Watai-Nishii J
    4. Tokai-Nishizumi N
    5. Yamamoto T
    6. Toyoshima YY

    (2003) The human chromokinesin Kid is a plus end-directed microtubule-based motor

    The EMBO Journal 22:1067–1074.

    https://doi.org/10.1093/emboj/cdg102

    • PubMed
    • Google Scholar
99. 1. Zhang P
    2. Knowles BA
    3. Goldstein LS
    4. Hawley RS

    (1990) A kinesin-like protein required for distributive chromosome segregation in Drosophila

    Cell 62:1053–1062.

    https://doi.org/10.1016/0092-8674(90)90383-p

    • PubMed
    • Google Scholar

Author details

1. Alex F Thompson

   Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, United States

   Contribution

   Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Writing - original draft, Writing – review and editing

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0003-4316-7532

2. Patrick R Blackburn

   1. Laboratory Medicine and Pathology, Mayo Clinic, Rochester, United States
   2. Pathology, St. Jude Children’s Research Hospital, Memphis, United States

   Contribution

   Data curation, Formal analysis, Investigation, Writing – review and editing

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0003-0658-1275

3. Noah S Arons

   Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, United States

   Contribution

   Formal analysis, Investigation

   Competing interests

   No competing interests declared

4. Sarah N Stevens

   Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, United States

   Contribution

   Formal analysis, Investigation

   Competing interests

   No competing interests declared

5. Dusica Babovic-Vuksanovic

   1. Laboratory Medicine and Pathology, Mayo Clinic, Rochester, United States
   2. Clinical Genomics, Mayo Clinic, Rochester, United States

   Contribution

   Formal analysis, Investigation, Writing – review and editing

   Competing interests

   No competing interests declared

6. Jane B Lian

   Department of Biochemistry, University of Vermont, Burlington, United States

   Contribution

   Conceptualization, Supervision, Writing – review and editing

   Competing interests

   No competing interests declared

7. Eric W Klee

   Biomedical Informatics, Mayo Clinic, Rochester, United States

   Contribution

   Conceptualization, Formal analysis, Writing – review and editing

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0003-2946-5795

8. Jason Stumpff

   Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, United States

   Contribution

   Conceptualization, Funding acquisition, Methodology, Writing - original draft, Writing – review and editing

   For correspondence

   jstumpff@uvm.edu

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0003-0392-1254

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