PPP1R35 is a novel centrosomal protein that regulates centriole length in concert with the microcephaly protein RTTN

  1. Andrew Michael Sydor
  2. Etienne Coyaud
  3. Cristina Rovelli
  4. Estelle Laurent
  5. Helen Liu
  6. Brian Raught
  7. Vito Mennella  Is a corresponding author
  1. The Hospital for Sick Children, Canada
  2. University Health Network, Canada

Abstract

Centrosome structure, function, and number are finely regulated at the cellular level to ensure normal mammalian development. Here, we characterize PPP1R35 as a novel bona fide centrosomal protein and demonstrate that it is critical for centriole elongation. Using quantitative super-resolution microscopy mapping and live-cell imaging we show that PPP1R35 is a resident centrosomal protein located in the proximal lumen above the cartwheel, a region of the centriole that has eluded detailed characterization. Loss of PPP1R35 function results in decreased centrosome number and shortened centrioles that lack centriolar distal and microtubule wall associated proteins required for centriole elongation. We further demonstrate that PPP1R35 acts downstream of, and forms a complex with, RTTN, a microcephaly protein required for distal centriole elongation. Altogether, our study identifies a novel step in the centriole elongation pathway centered on PPP1R35 and elucidates downstream partners of the microcephaly protein RTTN.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Andrew Michael Sydor

    Cell Biology Program, The Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3585-0446
  2. Etienne Coyaud

    Princess Margaret Cancer Centre, University Health Network, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Cristina Rovelli

    Cell Biology Program, The Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3171-6696
  4. Estelle Laurent

    Princess Margaret Cancer Centre, University Health Network, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Helen Liu

    Cell Biology Program, The Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Brian Raught

    Princess Margaret Cancer Centre, University Health Network, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Vito Mennella

    Cell Biology Program, The Hospital for Sick Children, Toronto, Canada
    For correspondence
    mennellalaboratory@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4842-9012

Funding

National Science and Engineering Research Council of Canada (Discovery grant RGPIN-2015-04795)

  • Vito Mennella

The Hospital for Sick Children (Restracomp Postdoctoral Fellowship)

  • Andrew Michael Sydor

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: April 26, 2018
  2. Accepted: August 21, 2018
  3. Accepted Manuscript published: August 31, 2018 (version 1)
  4. Version of Record published: September 17, 2018 (version 2)

Copyright

© 2018, Sydor 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.

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  1. Andrew Michael Sydor
  2. Etienne Coyaud
  3. Cristina Rovelli
  4. Estelle Laurent
  5. Helen Liu
  6. Brian Raught
  7. Vito Mennella
(2018)
PPP1R35 is a novel centrosomal protein that regulates centriole length in concert with the microcephaly protein RTTN
eLife 7:e37846.
https://doi.org/10.7554/eLife.37846

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