SSNA1 stabilizes dynamic microtubules and detects microtubule damage
- 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.
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All data generated or analyzed during this study are included in the manuscript and supporting files.
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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.
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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SSNA1 stabilizes dynamic microtubules and detects microtubule damage
eLife 10:e67282.
https://doi.org/10.7554/eLife.67282
