1. Cell Biology
  2. Computational and Systems Biology
Download icon

Human kinetochores are swivel joints that mediate microtubule attachments

  1. Chris A Smith
  2. Andrew D McAinsh  Is a corresponding author
  3. Nigel J Burroughs  Is a corresponding author
  1. University of Warwick, United Kingdom
Short Report
  • Cited 16
  • Views 2,088
  • Annotations
Cite this article as: eLife 2016;5:e16159 doi: 10.7554/eLife.16159

Abstract

Chromosome segregation is a mechanical process that requires assembly of the mitotic spindle - a dynamic microtubule-based force-generating machine. Connections to this spindle are mediated by sister kinetochore pairs, that form dynamic end-on attachments to microtubules emanating from opposite spindle poles. This bi-orientation generates forces that have been reported to stretch the kinetochore itself, which has been suggested to silence the spindle checkpoint and allow anaphase onset. We reveal using three dimensional tracking that the outer kinetochore domain can swivel around the inner kinetochore/centromere, which results in large reductions in intra-kinetochore distance (delta) when viewed in lower dimensions. We show that swivel provides a mechanical flexibility that enables kinetochores at the periphery of the spindle to engage microtubules. Swivel rather than delta reduces as cells approach anaphase, suggesting an organisational change linked to checkpoint satisfaction and/or obligatory changes in kinetochore mechanochemistry may occur before dissolution of sister chromatid cohesion.

Article and author information

Author details

  1. Chris A Smith

    Centre for Mechanochemical Cell Biology, Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Andrew D McAinsh

    Centre for Mechanochemical Cell Biology, Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, United Kingdom
    For correspondence
    A.D.McAinsh@warwick.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6808-0711
  3. Nigel J Burroughs

    Warwick Systems Biology Centre, Mathematics Institute, University of Warwick, Coventry, United Kingdom
    For correspondence
    N.J.Burroughs@warwick.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Funding

Engineering and Physical Sciences Research Council (EP/F500378/1)

  • Chris A Smith

Wellcome (106151/Z/14/Z)

  • Andrew D McAinsh

Biotechnology and Biological Sciences Research Council (BB/I021353/1)

  • Andrew D McAinsh
  • Nigel J Burroughs

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

Reviewing Editor

  1. Andrea Musacchio, Max Planck Institute of Molecular Physiology, Germany

Publication history

  1. Received: March 18, 2016
  2. Accepted: September 2, 2016
  3. Accepted Manuscript published: September 3, 2016 (version 1)
  4. Version of Record published: October 4, 2016 (version 2)

Copyright

© 2016, Smith 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

  • 2,088
    Page views
  • 669
    Downloads
  • 16
    Citations

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

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)

Further reading

    1. Biochemistry and Chemical Biology
    2. Cell Biology
    Zdravka Daneva et al.
    Research Article Updated

    Pannexin 1 (Panx1), an ATP-efflux pathway, has been linked with inflammation in pulmonary capillaries. However, the physiological roles of endothelial Panx1 in the pulmonary vasculature are unknown. Endothelial transient receptor potential vanilloid 4 (TRPV4) channels lower pulmonary artery (PA) contractility and exogenous ATP activates endothelial TRPV4 channels. We hypothesized that endothelial Panx1–ATP–TRPV4 channel signaling promotes vasodilation and lowers pulmonary arterial pressure (PAP). Endothelial, but not smooth muscle, knockout of Panx1 increased PA contractility and raised PAP in mice. Flow/shear stress increased ATP efflux through endothelial Panx1 in PAs. Panx1-effluxed extracellular ATP signaled through purinergic P2Y2 receptor (P2Y2R) to activate protein kinase Cα (PKCα), which in turn activated endothelial TRPV4 channels. Finally, caveolin-1 provided a signaling scaffold for endothelial Panx1, P2Y2R, PKCα, and TRPV4 channels in PAs, promoting their spatial proximity and enabling signaling interactions. These results indicate that endothelial Panx1–P2Y2R–TRPV4 channel signaling, facilitated by caveolin-1, reduces PA contractility and lowers PAP in mice.

    1. Cell Biology
    Adria Razzauti, Patrick FM Laurent
    Research Article

    Cilia are sensory organelles protruding from cell surfaces. Release of Extracellular Vesicles (EVs) from cilia was previously observed in mammals, Chlamydomonas, and in male C. elegans. Using the EV marker TSP-6 (an ortholog of mammalian CD9) and other ciliary receptors, we show that EVs are formed from ciliated sensory neurons in C. elegans hermaphrodites. Release of EVs is observed from two ciliary locations: the cilia tip and/or Periciliary Membrane Compartment (PCMC). Outward budding of EVs from the cilia tip leads to their release into the environment. EVs budding from the PCMC are concomitantly phagocytosed by the associated glial cells. To maintain cilia composition, a tight regulation of cargo import and removal is achieved by the action of Intra-Flagellar Transport (IFT). Unbalanced IFT due to cargo overexpression or mutations in the IFT machinery leads to local accumulation of ciliary proteins. Disposal of excess ciliary proteins via EVs reduces their local accumulation and exports them to the environment and/or to the glia associated to these ciliated neurons. We suggest that EV budding from cilia subcompartments acts as a safeguard mechanism to remove deleterious excess of ciliary material.