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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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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. |
format | Online Article Text |
id | pubmed-6879320 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
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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