摘要
Integrin receptors and their extracellular matrix ligands provide cues to cell proliferation, survival, differentiation and migration. Here, we show that alpha 2 beta 1 integrin, when ligated to the basement membrane component laminin-1, triggers a proliferation arrest in primary endothelial cells. Indeed, in the presence of strong growth signals supplied by growth factors and fibronectin, alpha 2 beta 1 engagement alters assembly of mature focal adhesions by alpha 5 beta 1 and leads to impairment of downstream signaling and cell-cycle arrest in the G1 phase. Although the capacity of alpha 5 beta 1 to signal for GTP loading of Rac is preserved, the joint engagement of alpha 2 beta 1 interferes with membrane anchorage of Rac. Adapting the 'split-ubiquitin' sensor to screen for membrane-proximal alpha 2 integrin partners, we identified the CD9 tetraspanin and further establish its requirement for destabilization of focal adhesions, control of Rac subcellular localization and growth arrest induced by alpha 2 beta 1 integrin. Altogether, our data establish that alpha 2 beta 1 integrin controls endothelial cell commitment towards quiescence by triggering a CD9-dependent dominant signaling.
- 出版日期2010-7-15