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SSNA1 stabilizes dynamic microtubules and detects microtubule damage

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...

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Autores principales: Lawrence, Elizabeth J, Arpag, Goker, Arnaiz, Cayetana, Zanic, Marija
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8798045/
https://www.ncbi.nlm.nih.gov/pubmed/34970964
http://dx.doi.org/10.7554/eLife.67282
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author Lawrence, Elizabeth J
Arpag, Goker
Arnaiz, Cayetana
Zanic, Marija
author_facet Lawrence, Elizabeth J
Arpag, Goker
Arnaiz, Cayetana
Zanic, Marija
author_sort Lawrence, Elizabeth J
collection PubMed
description 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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spelling pubmed-87980452022-01-31 SSNA1 stabilizes dynamic microtubules and detects microtubule damage Lawrence, Elizabeth J Arpag, Goker Arnaiz, Cayetana Zanic, Marija eLife Cell Biology 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. eLife Sciences Publications, Ltd 2021-12-31 /pmc/articles/PMC8798045/ /pubmed/34970964 http://dx.doi.org/10.7554/eLife.67282 Text en © 2021, Lawrence et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Lawrence, Elizabeth J
Arpag, Goker
Arnaiz, Cayetana
Zanic, Marija
SSNA1 stabilizes dynamic microtubules and detects microtubule damage
title SSNA1 stabilizes dynamic microtubules and detects microtubule damage
title_full SSNA1 stabilizes dynamic microtubules and detects microtubule damage
title_fullStr SSNA1 stabilizes dynamic microtubules and detects microtubule damage
title_full_unstemmed SSNA1 stabilizes dynamic microtubules and detects microtubule damage
title_short SSNA1 stabilizes dynamic microtubules and detects microtubule damage
title_sort ssna1 stabilizes dynamic microtubules and detects microtubule damage
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8798045/
https://www.ncbi.nlm.nih.gov/pubmed/34970964
http://dx.doi.org/10.7554/eLife.67282
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