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Integrin Mechano-chemical Signaling Generates Plasma Membrane Nanodomains that Promote Cell Spreading

Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are a major class of lipid-anchored plasma membrane proteins. GPI-APs form nanoclusters generated by cortical acto-myosin activity. While our understanding of the physical principles governing this process is emerging, the molecular machinery...

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Autores principales: Kalappurakkal, Joseph Mathew, Anilkumar, Anupama Ambika, Patra, Chandrima, van Zanten, Thomas S., Sheetz, Michael P., Mayor, Satyajit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879320/
https://www.ncbi.nlm.nih.gov/pubmed/31104842
http://dx.doi.org/10.1016/j.cell.2019.04.037
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author Kalappurakkal, Joseph Mathew
Anilkumar, Anupama Ambika
Patra, Chandrima
van Zanten, Thomas S.
Sheetz, Michael P.
Mayor, Satyajit
author_facet Kalappurakkal, Joseph Mathew
Anilkumar, Anupama Ambika
Patra, Chandrima
van Zanten, Thomas S.
Sheetz, Michael P.
Mayor, Satyajit
author_sort Kalappurakkal, Joseph Mathew
collection PubMed
description Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are a major class of lipid-anchored plasma membrane proteins. GPI-APs form nanoclusters generated by cortical acto-myosin activity. While our understanding of the physical principles governing this process is emerging, the molecular machinery and functional relevance of GPI-AP nanoclustering are unknown. Here, we first show that a membrane receptor signaling pathway directs nanocluster formation. Arg-Gly-Asp motif-containing ligands bound to the β1-integrin receptor activate src and focal adhesion kinases, resulting in RhoA signaling. This cascade triggers actin-nucleation via specific formins, which, along with myosin activity, drive the nanoclustering of membrane proteins with actin-binding domains. Concurrently, talinmediated activation of the mechano-transducer vinculin is required for the coupling of the acto-myosin machinery to inner-leaflet lipids, thereby generating GPI-AP nanoclusters. Second, we show that these nanoclusters are functional; disruption of their formation either in GPI-anchor remodeling mutants or in vinculin mutants impairs cell spreading and migration, hallmarks of integrin function.
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spelling pubmed-68793202019-11-26 Integrin Mechano-chemical Signaling Generates Plasma Membrane Nanodomains that Promote Cell Spreading Kalappurakkal, Joseph Mathew Anilkumar, Anupama Ambika Patra, Chandrima van Zanten, Thomas S. Sheetz, Michael P. Mayor, Satyajit Cell Article Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are a major class of lipid-anchored plasma membrane proteins. GPI-APs form nanoclusters generated by cortical acto-myosin activity. While our understanding of the physical principles governing this process is emerging, the molecular machinery and functional relevance of GPI-AP nanoclustering are unknown. Here, we first show that a membrane receptor signaling pathway directs nanocluster formation. Arg-Gly-Asp motif-containing ligands bound to the β1-integrin receptor activate src and focal adhesion kinases, resulting in RhoA signaling. This cascade triggers actin-nucleation via specific formins, which, along with myosin activity, drive the nanoclustering of membrane proteins with actin-binding domains. Concurrently, talinmediated activation of the mechano-transducer vinculin is required for the coupling of the acto-myosin machinery to inner-leaflet lipids, thereby generating GPI-AP nanoclusters. Second, we show that these nanoclusters are functional; disruption of their formation either in GPI-anchor remodeling mutants or in vinculin mutants impairs cell spreading and migration, hallmarks of integrin function. 2019-11-01 2019-05-16 /pmc/articles/PMC6879320/ /pubmed/31104842 http://dx.doi.org/10.1016/j.cell.2019.04.037 Text en http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kalappurakkal, Joseph Mathew
Anilkumar, Anupama Ambika
Patra, Chandrima
van Zanten, Thomas S.
Sheetz, Michael P.
Mayor, Satyajit
Integrin Mechano-chemical Signaling Generates Plasma Membrane Nanodomains that Promote Cell Spreading
title Integrin Mechano-chemical Signaling Generates Plasma Membrane Nanodomains that Promote Cell Spreading
title_full Integrin Mechano-chemical Signaling Generates Plasma Membrane Nanodomains that Promote Cell Spreading
title_fullStr Integrin Mechano-chemical Signaling Generates Plasma Membrane Nanodomains that Promote Cell Spreading
title_full_unstemmed Integrin Mechano-chemical Signaling Generates Plasma Membrane Nanodomains that Promote Cell Spreading
title_short Integrin Mechano-chemical Signaling Generates Plasma Membrane Nanodomains that Promote Cell Spreading
title_sort integrin mechano-chemical signaling generates plasma membrane nanodomains that promote cell spreading
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879320/
https://www.ncbi.nlm.nih.gov/pubmed/31104842
http://dx.doi.org/10.1016/j.cell.2019.04.037
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