
@article {59720,
	title = {Integrin Mechano-chemical Signaling Generates Plasma Membrane Nanodomains that Promote Cell Spreading.},
	journal = {Cell},
	volume = {177},
	year = {2019},
	month = {2019 Jun 13},
	pages = {1738-1756.e23},
	abstract = {<p>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, talin-mediated 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.</p>
},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2019.04.037},
	author = {Kalappurakkal, Joseph Mathew and Anilkumar, Anupama Ambika and Patra, Chandrima and van Zanten, Thomas S and Sheetz, Michael P and Mayor, Satyajit}
}
