期刊
CELL
卷 177, 期 7, 页码 1738-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2019.04.037
关键词
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资金
- NCBS-TIFR
- DST-SERB (Government of India)
- EMBO fellowship [ALTF 1519-2013]
- NCBS Campus fellowship
- JC Bose Fellowship from DST (Government of India)
- NCBS-Max Planck Lipid Centre
- HFSP [RGP0027/2012]
- Wellcome Trust/DBT India Alliance Margdarshi Fellowship [IA/M/15/1/502018]
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 beta 1-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.
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