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Dynein pulling forces counteract lamin-mediated nuclear stability during nuclear envelope repair
Recent work done exclusively in tissue culture cells revealed that the nuclear envelope (NE) ruptures and repairs in interphase. The duration of NE ruptures depends on lamins; however, the underlying mechanisms and relevance to in vivo events are not known. Here, we use the Caenorhabditis elegans zy...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5905298/ https://www.ncbi.nlm.nih.gov/pubmed/29386297 http://dx.doi.org/10.1091/mbc.E17-06-0374 |
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author | Penfield, Lauren Wysolmerski, Brian Mauro, Michael Farhadifar, Reza Martinez, Michael A. Biggs, Ronald Wu, Hai-Yin Broberg, Curtis Needleman, Daniel Bahmanyar, Shirin |
author_facet | Penfield, Lauren Wysolmerski, Brian Mauro, Michael Farhadifar, Reza Martinez, Michael A. Biggs, Ronald Wu, Hai-Yin Broberg, Curtis Needleman, Daniel Bahmanyar, Shirin |
author_sort | Penfield, Lauren |
collection | PubMed |
description | Recent work done exclusively in tissue culture cells revealed that the nuclear envelope (NE) ruptures and repairs in interphase. The duration of NE ruptures depends on lamins; however, the underlying mechanisms and relevance to in vivo events are not known. Here, we use the Caenorhabditis elegans zygote to analyze lamin’s role in NE rupture and repair in vivo. Transient NE ruptures and subsequent NE collapse are induced by weaknesses in the nuclear lamina caused by expression of an engineered hypomorphic C. elegans lamin allele. Dynein-generated forces that position nuclei enhance the severity of transient NE ruptures and cause NE collapse. Reduction of dynein forces allows the weakened lamin network to restrict nucleo–cytoplasmic mixing and support stable NE recovery. Surprisingly, the high incidence of transient NE ruptures does not contribute to embryonic lethality, which is instead correlated with stochastic chromosome scattering resulting from premature NE collapse, suggesting that C. elegans tolerates transient losses of NE compartmentalization during early embryogenesis. In sum, we demonstrate that lamin counteracts dynein forces to promote stable NE repair and prevent catastrophic NE collapse, and thus provide the first mechanistic analysis of NE rupture and repair in an organismal context. |
format | Online Article Text |
id | pubmed-5905298 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-59052982018-06-16 Dynein pulling forces counteract lamin-mediated nuclear stability during nuclear envelope repair Penfield, Lauren Wysolmerski, Brian Mauro, Michael Farhadifar, Reza Martinez, Michael A. Biggs, Ronald Wu, Hai-Yin Broberg, Curtis Needleman, Daniel Bahmanyar, Shirin Mol Biol Cell Articles Recent work done exclusively in tissue culture cells revealed that the nuclear envelope (NE) ruptures and repairs in interphase. The duration of NE ruptures depends on lamins; however, the underlying mechanisms and relevance to in vivo events are not known. Here, we use the Caenorhabditis elegans zygote to analyze lamin’s role in NE rupture and repair in vivo. Transient NE ruptures and subsequent NE collapse are induced by weaknesses in the nuclear lamina caused by expression of an engineered hypomorphic C. elegans lamin allele. Dynein-generated forces that position nuclei enhance the severity of transient NE ruptures and cause NE collapse. Reduction of dynein forces allows the weakened lamin network to restrict nucleo–cytoplasmic mixing and support stable NE recovery. Surprisingly, the high incidence of transient NE ruptures does not contribute to embryonic lethality, which is instead correlated with stochastic chromosome scattering resulting from premature NE collapse, suggesting that C. elegans tolerates transient losses of NE compartmentalization during early embryogenesis. In sum, we demonstrate that lamin counteracts dynein forces to promote stable NE repair and prevent catastrophic NE collapse, and thus provide the first mechanistic analysis of NE rupture and repair in an organismal context. The American Society for Cell Biology 2018-04-01 /pmc/articles/PMC5905298/ /pubmed/29386297 http://dx.doi.org/10.1091/mbc.E17-06-0374 Text en © 2018 Penfield et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0/ This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License. |
spellingShingle | Articles Penfield, Lauren Wysolmerski, Brian Mauro, Michael Farhadifar, Reza Martinez, Michael A. Biggs, Ronald Wu, Hai-Yin Broberg, Curtis Needleman, Daniel Bahmanyar, Shirin Dynein pulling forces counteract lamin-mediated nuclear stability during nuclear envelope repair |
title | Dynein pulling forces counteract lamin-mediated nuclear stability during nuclear envelope repair |
title_full | Dynein pulling forces counteract lamin-mediated nuclear stability during nuclear envelope repair |
title_fullStr | Dynein pulling forces counteract lamin-mediated nuclear stability during nuclear envelope repair |
title_full_unstemmed | Dynein pulling forces counteract lamin-mediated nuclear stability during nuclear envelope repair |
title_short | Dynein pulling forces counteract lamin-mediated nuclear stability during nuclear envelope repair |
title_sort | dynein pulling forces counteract lamin-mediated nuclear stability during nuclear envelope repair |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5905298/ https://www.ncbi.nlm.nih.gov/pubmed/29386297 http://dx.doi.org/10.1091/mbc.E17-06-0374 |
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