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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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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. |
format | Online Article Text |
id | pubmed-8798045 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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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