1. Cell Biology
Download icon

Male meiotic spindle features that efficiently segregate paired and lagging chromosomes

  1. Gunar Fabig  Is a corresponding author
  2. Robert Kiewisz
  3. Norbert Lindow
  4. James A Powers
  5. Vanessa Cota
  6. Luis J Quintanilla
  7. Jan Brugués
  8. Steffen Prohaska
  9. Diana S Chu
  10. Thomas Müller-Reichert  Is a corresponding author
  1. Technische Universität Dresden, Germany
  2. Zuse Institute Berlin, Germany
  3. Indiana University, United States
  4. San Francisco State University, United States
  5. Max Planck Institute, Germany
Research Article
  • Cited 5
  • Views 1,591
  • Annotations
Cite this article as: eLife 2020;9:e50988 doi: 10.7554/eLife.50988

Abstract

Chromosome segregation during male meiosis is tailored to rapidly generate multitudes of sperm. Little is known about mechanisms that efficiently partition chromosomes to produce sperm. Using live imaging and tomographic reconstructions of spermatocyte meiotic spindles in Caenorhabditis elegans, we find the lagging X chromosome, a distinctive feature of anaphase I in C. elegans males, is due to lack of chromosome pairing. The unpaired chromosome remains tethered to centrosomes by lengthening kinetochore microtubules, which are under tension, suggesting that a 'tug of war' reliably resolves lagging. We find spermatocytes exhibit simultaneous pole-to-chromosome shortening (anaphase A) and pole-to-pole elongation (anaphase B). Electron tomography unexpectedly revealed spermatocyte anaphase A does not stem solely from kinetochore microtubule shortening. Instead, movement of autosomes is largely driven by distance change between chromosomes, microtubules, and centrosomes upon tension release during anaphase. Overall, we define novel features that segregate both lagging and paired chromosomes for optimal sperm production.

Data availability

Data have been uploaded to the TU Dresden Open Access Repository and Archive system (OpARA) and are available as open access: http://dx.doi.org/10.25532/OPARA-56

The following data sets were generated

Article and author information

Author details

  1. Gunar Fabig

    Experimental Center, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
    For correspondence
    gunar.fabig@tu-dresden.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3017-0978

  2. Robert Kiewisz

    Experimental Center, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2733-4978

  3. Norbert Lindow

    Visualization and Data Analysis, Zuse Institute Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.

  4. James A Powers

    Light Microscopy Imaging Center, Indiana University, Bloomington, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Vanessa Cota

    Department of Biology, San Francisco State University, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Luis J Quintanilla

    Department of Biology, San Francisco State University, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Jan Brugués

    Molecular Cell Biology and Genetics, Max Planck Institute, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.

  8. Steffen Prohaska

    Visualization and Data Analysis, Zuse Institute Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.

  9. Diana S Chu

    Department of Biology, San Francisco State University, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  10. Thomas Müller-Reichert

    Experimental Center, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
    For correspondence
    mueller-reichert@tu-dresden.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0203-1436

Funding

Deutsche Forschungsgemeinschaft (MU 1423/10-1)

  • Gunar Fabig
  • Thomas Müller-Reichert

Horizon 2020 Framework Programme (No. 675737)

  • Robert Kiewisz
  • Thomas Müller-Reichert

National Institutes of Health (R03 HD093990-01A1)

  • Vanessa Cota
  • Diana S Chu

National Science Foundation (RUI-1817611,DBI-1548297)

  • Vanessa Cota
  • Diana S Chu

National Institutes of Health (NIH1S10OD024988-01)

  • James A Powers

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Yukiko M Yamashita, University of Michigan, United States

Publication history

  1. Received: August 9, 2019
  2. Accepted: March 8, 2020
  3. Accepted Manuscript published: March 9, 2020 (version 1)
  4. Accepted Manuscript updated: March 10, 2020 (version 2)
  5. Version of Record published: March 27, 2020 (version 3)
  6. Version of Record updated: April 1, 2020 (version 4)

Copyright

© 2020, Fabig et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,591
    Page views
  • 299
    Downloads
  • 5
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Categories and tags

Research organism

Further reading

    1. Cell Biology

    A MET-PTPRK kinase-phosphatase rheostat controls ZNRF3 and Wnt signaling

    Minseong Kim et al.
    Research Advance Updated

    Zinc and ring finger 3 (ZNRF3) is a transmembrane E3 ubiquitin ligase that targets Wnt receptors for ubiquitination and lysosomal degradation. Previously, we showed that dephosphorylation of an endocytic tyrosine motif (4Y motif) in ZNRF3 by protein tyrosine phosphatase receptor-type kappa (PTPRK) promotes ZNRF3 internalization and Wnt receptor degradation (Chang et al 2020). However, a responsible protein tyrosine kinase(s) (PTK) phosphorylating the 4Y motif remained elusive. Here we identify the proto-oncogene MET (mesenchymal-epithelial transition factor) as a 4Y kinase. MET binds to ZNRF3 and induces 4Y phosphorylation, stimulated by the MET ligand HGF (hepatocyte growth factor, scatter factor). HGF-MET signaling reduces ZNRF3-dependent Wnt receptor degradation thereby enhancing Wnt/β-catenin signaling. Conversely, depletion or pharmacological inhibition of MET promotes the internalization of ZNRF3 and Wnt receptor degradation. We conclude that HGF-MET signaling phosphorylates- and PTPRK dephosphorylates ZNRF3 to regulate ZNRF3 internalization, functioning as a rheostat for Wnt signaling that may offer novel opportunities for therapeutic intervention.

    1. Cell Biology
    2. Developmental Biology

    Par3 cooperates with Sanpodo for the assembly of Notch clusters following asymmetric division of Drosophila sensory organ precursor cells

    Elise Houssin et al.
    Research Article Updated

    In multiple cell lineages, Delta-Notch signalling regulates cell fate decisions owing to unidirectional signalling between daughter cells. In Drosophila pupal sensory organ lineage, Notch regulates the intra-lineage pIIa/pIIb fate decision at cytokinesis. Notch and Delta that localise apically and basally at the pIIa-pIIb interface are expressed at low levels and their residence time at the plasma membrane is in the order of minutes. How Delta can effectively interact with Notch to trigger signalling from a large plasma membrane area remains poorly understood. Here, we report that the signalling interface possesses a unique apico-basal polarity with Par3/Bazooka localising in the form of nano-clusters at the apical and basal level. Notch is preferentially targeted to the pIIa-pIIb interface, where it co-clusters with Bazooka and its cofactor Sanpodo. Clusters whose assembly relies on Bazooka and Sanpodo activities are also positive for Neuralized, the E3 ligase required for Delta activity. We propose that the nano-clusters act as snap buttons at the new pIIa-pIIb interface to allow efficient intra-lineage signalling.

    1. Cell Biology
    2. Neuroscience

    TRPM7 is critical for short-term synaptic depression by regulating synaptic vesicle endocytosis

    Zhong-Jiao Jiang et al.
    Research Article Updated

    Transient receptor potential melastatin 7 (TRPM7) contributes to a variety of physiological and pathological processes in many tissues and cells. With a widespread distribution in the nervous system, TRPM7 is involved in animal behaviors and neuronal death induced by ischemia. However, the physiological role of TRPM7 in central nervous system (CNS) neuron remains unclear. Here, we identify endocytic defects in neuroendocrine cells and neurons from TRPM7 knockout (KO) mice, indicating a role of TRPM7 in synaptic vesicle endocytosis. Our experiments further pinpoint the importance of TRPM7 as an ion channel in synaptic vesicle endocytosis. Ca2+ imaging detects a defect in presynaptic Ca2+ dynamics in TRPM7 KO neuron, suggesting an importance of Ca2+ influx via TRPM7 in synaptic vesicle endocytosis. Moreover, the short-term depression is enhanced in both excitatory and inhibitory synaptic transmissions from TRPM7 KO mice. Taken together, our data suggests that Ca2+ influx via TRPM7 may be critical for short-term plasticity of synaptic strength by regulating synaptic vesicle endocytosis in neurons.