The KASH5 protein involved in meiotic chromosomal movements is a novel dynein activating adaptor

  1. Ritvija Agrawal
  2. John P Gillies
  3. Juliana L Zang
  4. Jingjing Zhang
  5. Sharon R Garrott
  6. Hiroki Shibuya  Is a corresponding author
  7. Jayakrishnan Nandakumar  Is a corresponding author
  8. Morgan E DeSantis  Is a corresponding author
  1. University of Michigan-Ann Arbor, United States
  2. University of Gothenburg, Sweden

Abstract

Dynein harnesses ATP hydrolysis to move cargo on microtubules in multiple biological contexts. Dynein meets a unique challenge in meiosis by moving chromosomes tethered to the nuclear envelope to facilitate homolog pairing essential for gametogenesis. Though processive dynein motility requires binding to an activating adaptor, the identity of the activating adaptor required for dynein to move meiotic chromosomes is unknown. We show that the meiosis-specific nuclear-envelope protein KASH5 is a dynein activating adaptor: KASH5 directly binds dynein using a mechanism conserved among activating adaptors and converts dynein into a processive motor. We map the dynein-binding surface of KASH5, identifying mutations that abrogate dynein binding in vitro and disrupt recruitment of the dynein machinery to the nuclear envelope in cultured cells and mouse spermatocytes in vivo. Our study identifies KASH5 as the first transmembrane dynein activating adaptor and provides molecular insights into how it activates dynein during meiosis.

Data availability

Source data for TIRF experiments in Figure 3-6 are found in the file "Agrawal_etal_Source data" and labeled appropriately.All custom macros written for this study (used in Figure 5) are available on GitHub (https://github.com/DeSantis-Lab/Nuclear_Envelope_Localization_Macros)

The following data sets were generated

Article and author information

Author details

  1. Ritvija Agrawal

    Department of Molecular, Cellular and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. John P Gillies

    Department of Molecular, Cellular and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Juliana L Zang

    Department of Molecular, Cellular and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5738-8355
  4. Jingjing Zhang

    Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  5. Sharon R Garrott

    Department of Molecular, Cellular and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Hiroki Shibuya

    Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
    For correspondence
    hiroki.shibuya@gu.se
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3400-0741
  7. Jayakrishnan Nandakumar

    Department of Molecular, Cellular and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States
    For correspondence
    jknanda@umich.edu
    Competing interests
    The authors declare that no competing interests exist.
  8. Morgan E DeSantis

    Department of Molecular, Cellular and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States
    For correspondence
    mdesant@umich.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4096-8548

Funding

National Institutes of Health (R00-GM127757)

  • Morgan E DeSantis

National Institutes of Health (R01-GM120094)

  • Jayakrishnan Nandakumar

American Heart Association (RSG-17-037-01-DMC)

  • Jayakrishnan Nandakumar

European Research Council (StG-801659)

  • Hiroki Shibuya

Swedish Research Council (2018-03426)

  • Hiroki Shibuya

Knut och Alice Wallenbergs Stiftelse (KAW2019.0180)

  • Hiroki Shibuya

American Heart Association

  • Ritvija Agrawal

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

Reviewing Editor

  1. Ahmet Yildiz, University of California, Berkeley, United States

Ethics

Animal experimentation: All animal experiments were approved by and performed in compliance with the regulations at the University of Gothenburg Institutional Animal Care and Use Committee (#1316/18).

Version history

  1. Received: February 26, 2022
  2. Preprint posted: March 12, 2022 (view preprint)
  3. Accepted: June 14, 2022
  4. Accepted Manuscript published: June 15, 2022 (version 1)
  5. Version of Record published: June 29, 2022 (version 2)

Copyright

© 2022, Agrawal 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. Ritvija Agrawal
  2. John P Gillies
  3. Juliana L Zang
  4. Jingjing Zhang
  5. Sharon R Garrott
  6. Hiroki Shibuya
  7. Jayakrishnan Nandakumar
  8. Morgan E DeSantis
(2022)
The KASH5 protein involved in meiotic chromosomal movements is a novel dynein activating adaptor
eLife 11:e78201.
https://doi.org/10.7554/eLife.78201

Share this article

https://doi.org/10.7554/eLife.78201

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