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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2019
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.
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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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