Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Penfield, Lauren, Wysolmerski, Brian, Mauro, Michael, Farhadifar, Reza, Martinez, Michael A., Biggs, Ronald, Wu, Hai-Yin, Broberg, Curtis, Needleman, Daniel, Bahmanyar, Shirin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2018
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
_version_ 1783315244044517376
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
work_keys_str_mv AT penfieldlauren dyneinpullingforcescounteractlaminmediatednuclearstabilityduringnuclearenveloperepair
AT wysolmerskibrian dyneinpullingforcescounteractlaminmediatednuclearstabilityduringnuclearenveloperepair
AT mauromichael dyneinpullingforcescounteractlaminmediatednuclearstabilityduringnuclearenveloperepair
AT farhadifarreza dyneinpullingforcescounteractlaminmediatednuclearstabilityduringnuclearenveloperepair
AT martinezmichaela dyneinpullingforcescounteractlaminmediatednuclearstabilityduringnuclearenveloperepair
AT biggsronald dyneinpullingforcescounteractlaminmediatednuclearstabilityduringnuclearenveloperepair
AT wuhaiyin dyneinpullingforcescounteractlaminmediatednuclearstabilityduringnuclearenveloperepair
AT brobergcurtis dyneinpullingforcescounteractlaminmediatednuclearstabilityduringnuclearenveloperepair
AT needlemandaniel dyneinpullingforcescounteractlaminmediatednuclearstabilityduringnuclearenveloperepair
AT bahmanyarshirin dyneinpullingforcescounteractlaminmediatednuclearstabilityduringnuclearenveloperepair