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Role of KASH domain lengths in the regulation of LINC complexes
The linker of the nucleoskeleton and cytoskeleton (LINC) complex is formed by the conserved interactions between Sad-1 and UNC-84 (SUN) and Klarsicht, ANC-1, SYNE homology (KASH) domain proteins, providing a physical coupling between the nucleoskeleton and cytoskeleton that mediates the transfer of...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727767/ https://www.ncbi.nlm.nih.gov/pubmed/30995155 http://dx.doi.org/10.1091/mbc.E19-02-0079 |
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author | Jahed, Zeinab Hao, Hongyan Thakkar, Vyom Vu, Uyen T. Valdez, Venecia A. Rathish, Akshay Tolentino, Chris Kim, Samuel C. J. Fadavi, Darya Starr, Daniel A. Mofrad, Mohammad R. K. |
author_facet | Jahed, Zeinab Hao, Hongyan Thakkar, Vyom Vu, Uyen T. Valdez, Venecia A. Rathish, Akshay Tolentino, Chris Kim, Samuel C. J. Fadavi, Darya Starr, Daniel A. Mofrad, Mohammad R. K. |
author_sort | Jahed, Zeinab |
collection | PubMed |
description | The linker of the nucleoskeleton and cytoskeleton (LINC) complex is formed by the conserved interactions between Sad-1 and UNC-84 (SUN) and Klarsicht, ANC-1, SYNE homology (KASH) domain proteins, providing a physical coupling between the nucleoskeleton and cytoskeleton that mediates the transfer of physical forces across the nuclear envelope. The LINC complex can perform distinct cellular functions by pairing various KASH domain proteins with the same SUN domain protein. For example, in Caenorhabditis elegans, SUN protein UNC-84 binds to two KASH proteins UNC-83 and ANC-1 to mediate nuclear migration and anchorage, respectively. In addition to distinct cytoplasmic domains, the luminal KASH domain also varies among KASH domain proteins of distinct functions. In this study, we combined in vivo C. elegans genetics and in silico molecular dynamics simulations to understand the relation between the length and amino acid composition of the luminal KASH domain, and the function of the SUN–KASH complex. We show that longer KASH domains can withstand and transfer higher forces and interact with the membrane through a conserved membrane proximal EEDY domain that is unique to longer KASH domains. In agreement with our models, our in vivo results show that swapping the KASH domains of ANC-1 and UNC-83, or shortening the KASH domain of ANC-1, both result in a nuclear anchorage defect in C. elegans. |
format | Online Article Text |
id | pubmed-6727767 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-67277672019-10-07 Role of KASH domain lengths in the regulation of LINC complexes Jahed, Zeinab Hao, Hongyan Thakkar, Vyom Vu, Uyen T. Valdez, Venecia A. Rathish, Akshay Tolentino, Chris Kim, Samuel C. J. Fadavi, Darya Starr, Daniel A. Mofrad, Mohammad R. K. Mol Biol Cell Articles The linker of the nucleoskeleton and cytoskeleton (LINC) complex is formed by the conserved interactions between Sad-1 and UNC-84 (SUN) and Klarsicht, ANC-1, SYNE homology (KASH) domain proteins, providing a physical coupling between the nucleoskeleton and cytoskeleton that mediates the transfer of physical forces across the nuclear envelope. The LINC complex can perform distinct cellular functions by pairing various KASH domain proteins with the same SUN domain protein. For example, in Caenorhabditis elegans, SUN protein UNC-84 binds to two KASH proteins UNC-83 and ANC-1 to mediate nuclear migration and anchorage, respectively. In addition to distinct cytoplasmic domains, the luminal KASH domain also varies among KASH domain proteins of distinct functions. In this study, we combined in vivo C. elegans genetics and in silico molecular dynamics simulations to understand the relation between the length and amino acid composition of the luminal KASH domain, and the function of the SUN–KASH complex. We show that longer KASH domains can withstand and transfer higher forces and interact with the membrane through a conserved membrane proximal EEDY domain that is unique to longer KASH domains. In agreement with our models, our in vivo results show that swapping the KASH domains of ANC-1 and UNC-83, or shortening the KASH domain of ANC-1, both result in a nuclear anchorage defect in C. elegans. The American Society for Cell Biology 2019-07-22 /pmc/articles/PMC6727767/ /pubmed/30995155 http://dx.doi.org/10.1091/mbc.E19-02-0079 Text en © 2019 Jahed 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 Jahed, Zeinab Hao, Hongyan Thakkar, Vyom Vu, Uyen T. Valdez, Venecia A. Rathish, Akshay Tolentino, Chris Kim, Samuel C. J. Fadavi, Darya Starr, Daniel A. Mofrad, Mohammad R. K. Role of KASH domain lengths in the regulation of LINC complexes |
title | Role of KASH domain lengths in the regulation of LINC complexes |
title_full | Role of KASH domain lengths in the regulation of LINC complexes |
title_fullStr | Role of KASH domain lengths in the regulation of LINC complexes |
title_full_unstemmed | Role of KASH domain lengths in the regulation of LINC complexes |
title_short | Role of KASH domain lengths in the regulation of LINC complexes |
title_sort | role of kash domain lengths in the regulation of linc complexes |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727767/ https://www.ncbi.nlm.nih.gov/pubmed/30995155 http://dx.doi.org/10.1091/mbc.E19-02-0079 |
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