The distinct roles of the nucleus and nucleus-cytoskeleton connections in three-dimensional cell migration

Cells often migrate in vivo in an extracellular matrix that is intrinsically three-dimensional (3D) and the role of actin filament architecture in 3D cell migration is less well understood. Here we show that, while recently identified linkers of nucleoskeleton to cytoskeleton (LINC) complexes play a...

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Autores principales: Khatau, Shyam B., Bloom, Ryan J., Bajpai, Saumendra, Razafsky, David, Zang, Shu, Giri, Anjil, Wu, Pei-Hsun, Marchand, Jorge, Celedon, Alfredo, Hale, Christopher M., Sun, Sean X., Hodzic, Didier, Wirtz, Denis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2012
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388469/
https://www.ncbi.nlm.nih.gov/pubmed/22761994
http://dx.doi.org/10.1038/srep00488
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author Khatau, Shyam B.
Bloom, Ryan J.
Bajpai, Saumendra
Razafsky, David
Zang, Shu
Giri, Anjil
Wu, Pei-Hsun
Marchand, Jorge
Celedon, Alfredo
Hale, Christopher M.
Sun, Sean X.
Hodzic, Didier
Wirtz, Denis
author_facet Khatau, Shyam B.
Bloom, Ryan J.
Bajpai, Saumendra
Razafsky, David
Zang, Shu
Giri, Anjil
Wu, Pei-Hsun
Marchand, Jorge
Celedon, Alfredo
Hale, Christopher M.
Sun, Sean X.
Hodzic, Didier
Wirtz, Denis
author_sort Khatau, Shyam B.
collection PubMed
description Cells often migrate in vivo in an extracellular matrix that is intrinsically three-dimensional (3D) and the role of actin filament architecture in 3D cell migration is less well understood. Here we show that, while recently identified linkers of nucleoskeleton to cytoskeleton (LINC) complexes play a minimal role in conventional 2D migration, they play a critical role in regulating the organization of a subset of actin filament bundles – the perinuclear actin cap - connected to the nucleus through Nesprin2giant and Nesprin3 in cells in 3D collagen I matrix. Actin cap fibers prolong the nucleus and mediate the formation of pseudopodial protrusions, which drive matrix traction and 3D cell migration. Disruption of LINC complexes disorganizes the actin cap, which impairs 3D cell migration. A simple mechanical model explains why LINC complexes and the perinuclear actin cap are essential in 3D migration by providing mechanical support to the formation of pseudopodial protrusions.
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spelling pubmed-33884692012-07-03 The distinct roles of the nucleus and nucleus-cytoskeleton connections in three-dimensional cell migration Khatau, Shyam B. Bloom, Ryan J. Bajpai, Saumendra Razafsky, David Zang, Shu Giri, Anjil Wu, Pei-Hsun Marchand, Jorge Celedon, Alfredo Hale, Christopher M. Sun, Sean X. Hodzic, Didier Wirtz, Denis Sci Rep Article Cells often migrate in vivo in an extracellular matrix that is intrinsically three-dimensional (3D) and the role of actin filament architecture in 3D cell migration is less well understood. Here we show that, while recently identified linkers of nucleoskeleton to cytoskeleton (LINC) complexes play a minimal role in conventional 2D migration, they play a critical role in regulating the organization of a subset of actin filament bundles – the perinuclear actin cap - connected to the nucleus through Nesprin2giant and Nesprin3 in cells in 3D collagen I matrix. Actin cap fibers prolong the nucleus and mediate the formation of pseudopodial protrusions, which drive matrix traction and 3D cell migration. Disruption of LINC complexes disorganizes the actin cap, which impairs 3D cell migration. A simple mechanical model explains why LINC complexes and the perinuclear actin cap are essential in 3D migration by providing mechanical support to the formation of pseudopodial protrusions. Nature Publishing Group 2012-07-03 /pmc/articles/PMC3388469/ /pubmed/22761994 http://dx.doi.org/10.1038/srep00488 Text en Copyright © 2012, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareALike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Article
Khatau, Shyam B.
Bloom, Ryan J.
Bajpai, Saumendra
Razafsky, David
Zang, Shu
Giri, Anjil
Wu, Pei-Hsun
Marchand, Jorge
Celedon, Alfredo
Hale, Christopher M.
Sun, Sean X.
Hodzic, Didier
Wirtz, Denis
The distinct roles of the nucleus and nucleus-cytoskeleton connections in three-dimensional cell migration
title The distinct roles of the nucleus and nucleus-cytoskeleton connections in three-dimensional cell migration
title_full The distinct roles of the nucleus and nucleus-cytoskeleton connections in three-dimensional cell migration
title_fullStr The distinct roles of the nucleus and nucleus-cytoskeleton connections in three-dimensional cell migration
title_full_unstemmed The distinct roles of the nucleus and nucleus-cytoskeleton connections in three-dimensional cell migration
title_short The distinct roles of the nucleus and nucleus-cytoskeleton connections in three-dimensional cell migration
title_sort distinct roles of the nucleus and nucleus-cytoskeleton connections in three-dimensional cell migration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388469/
https://www.ncbi.nlm.nih.gov/pubmed/22761994
http://dx.doi.org/10.1038/srep00488
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