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The WAVE Regulatory Complex Is Required to Balance Protrusion and Adhesion in Migration

Cells migrating over 2D substrates are required to polymerise actin at the leading edge to form lamellipodia protrusions and nascent adhesions to anchor the protrusion to the substrate. The major actin nucleator in lamellipodia formation is the Arp2/3 complex, which is activated by the WAVE regulato...

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Autores principales: Whitelaw, Jamie A., Swaminathan, Karthic, Kage, Frieda, Machesky, Laura M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407199/
https://www.ncbi.nlm.nih.gov/pubmed/32646006
http://dx.doi.org/10.3390/cells9071635
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author Whitelaw, Jamie A.
Swaminathan, Karthic
Kage, Frieda
Machesky, Laura M.
author_facet Whitelaw, Jamie A.
Swaminathan, Karthic
Kage, Frieda
Machesky, Laura M.
author_sort Whitelaw, Jamie A.
collection PubMed
description Cells migrating over 2D substrates are required to polymerise actin at the leading edge to form lamellipodia protrusions and nascent adhesions to anchor the protrusion to the substrate. The major actin nucleator in lamellipodia formation is the Arp2/3 complex, which is activated by the WAVE regulatory complex (WRC). Using inducible Nckap1 floxed mouse embryonic fibroblasts (MEFs), we confirm that the WRC is required for lamellipodia formation, and importantly, for generating the retrograde flow of actin from the leading cell edge. The loss of NCKAP1 also affects cell spreading and focal adhesion dynamics. In the absence of lamellipodium, cells can become elongated and move with a single thin pseudopod, which appears devoid of N-WASP. This phenotype was more prevalent on collagen than fibronectin, where we observed an increase in migratory speed. Thus, 2D cell migration on collagen is less dependent on branched actin.
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spelling pubmed-74071992020-08-11 The WAVE Regulatory Complex Is Required to Balance Protrusion and Adhesion in Migration Whitelaw, Jamie A. Swaminathan, Karthic Kage, Frieda Machesky, Laura M. Cells Article Cells migrating over 2D substrates are required to polymerise actin at the leading edge to form lamellipodia protrusions and nascent adhesions to anchor the protrusion to the substrate. The major actin nucleator in lamellipodia formation is the Arp2/3 complex, which is activated by the WAVE regulatory complex (WRC). Using inducible Nckap1 floxed mouse embryonic fibroblasts (MEFs), we confirm that the WRC is required for lamellipodia formation, and importantly, for generating the retrograde flow of actin from the leading cell edge. The loss of NCKAP1 also affects cell spreading and focal adhesion dynamics. In the absence of lamellipodium, cells can become elongated and move with a single thin pseudopod, which appears devoid of N-WASP. This phenotype was more prevalent on collagen than fibronectin, where we observed an increase in migratory speed. Thus, 2D cell migration on collagen is less dependent on branched actin. MDPI 2020-07-07 /pmc/articles/PMC7407199/ /pubmed/32646006 http://dx.doi.org/10.3390/cells9071635 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Whitelaw, Jamie A.
Swaminathan, Karthic
Kage, Frieda
Machesky, Laura M.
The WAVE Regulatory Complex Is Required to Balance Protrusion and Adhesion in Migration
title The WAVE Regulatory Complex Is Required to Balance Protrusion and Adhesion in Migration
title_full The WAVE Regulatory Complex Is Required to Balance Protrusion and Adhesion in Migration
title_fullStr The WAVE Regulatory Complex Is Required to Balance Protrusion and Adhesion in Migration
title_full_unstemmed The WAVE Regulatory Complex Is Required to Balance Protrusion and Adhesion in Migration
title_short The WAVE Regulatory Complex Is Required to Balance Protrusion and Adhesion in Migration
title_sort wave regulatory complex is required to balance protrusion and adhesion in migration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407199/
https://www.ncbi.nlm.nih.gov/pubmed/32646006
http://dx.doi.org/10.3390/cells9071635
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