SSNA1 stabilizes dynamic microtubules and detects microtubule damage

  1. Elizabeth J Lawrence
  2. Goker Arpag
  3. Cayetana Arnaiz
  4. Marija Zanic  Is a corresponding author
  1. Vanderbilt University, United States

Abstract

Sjögren's Syndrome Nuclear Autoantigen 1 (SSNA1/NA14) is a microtubule-associated protein with important functions in cilia, dividing cells and developing neurons. However, the direct effects of SSNA1 on microtubules are not known. We employed in vitro reconstitution with purified proteins and TIRF microscopy to investigate the activity of human SSNA1 on dynamic microtubule ends and lattices. Our results show that SSNA1 modulates all parameters of microtubule dynamic instability - slowing down the rates of growth, shrinkage and catastrophe, and promoting rescue. We find that SSNA1 forms stretches along growing microtubule ends and binds cooperatively to the microtubule lattice. Furthermore, SSNA1 is enriched on microtubule damage sites, occurring both naturally, as well as induced by the microtubule severing enzyme spastin. Finally, SSNA1 binding protects microtubules against spastin's severing activity. Taken together, our results demonstrate that SSNA1 is both a potent microtubule stabilizing protein and a novel sensor of microtubule damage; activities that likely underlie SSNA1's functions on microtubule structures in cells.

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. Elizabeth J Lawrence

    Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Goker Arpag

    Department of Cell and Developmental Biology and Program in Developmental Biology, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6893-2678
  3. Cayetana Arnaiz

    Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Marija Zanic

    Department of Cell and Developmental Biology and Program in Developmental Biology, Vanderbilt University, Nashville, United States
    For correspondence
    marija.zanic@vanderbilt.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5127-5819

Funding

National Institutes of Health (T32CA119925)

  • Elizabeth J Lawrence

National Institutes of Health (R35GM119552)

  • Marija Zanic

National Science Foundation (MCB2018661)

  • Marija Zanic

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

Reviewing Editor

  1. Kassandra M Ori-McKenney, University of California, United States

Publication history

  1. Received: February 5, 2021
  2. Preprint posted: February 6, 2021 (view preprint)
  3. Accepted: December 30, 2021
  4. Accepted Manuscript published: December 31, 2021 (version 1)
  5. Version of Record published: January 27, 2022 (version 2)

Copyright

© 2021, Lawrence 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. Elizabeth J Lawrence
  2. Goker Arpag
  3. Cayetana Arnaiz
  4. Marija Zanic
(2021)
SSNA1 stabilizes dynamic microtubules and detects microtubule damage
eLife 10:e67282.
https://doi.org/10.7554/eLife.67282

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