Integrins control motile strategy through a Rho-cofilin pathway

被引:164
作者
Danen, EHJ [1 ]
van Rheenen, J [1 ]
Franken, W [1 ]
Huveneers, S [1 ]
Sonneveld, P [1 ]
Jalink, K [1 ]
Sonnenberg, A [1 ]
机构
[1] Netherlands Canc Inst, Div Cell Biol, NL-1066 CX Amsterdam, Netherlands
关键词
D O I
10.1083/jcb.200412081
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
During wound healing, angiogenesis, and tumor invasion, cells often change their expression profiles of fibronectin- binding integrins. Here, we show that beta 1 integrins promote random migration, whereas beta 3 integrins promote persistent migration in the same epithelial cell background. Adhesion to fibronectin by alpha v beta 3 supports extensive actin cytoskeletal reorganization through the actin-severing protein cofilin, resulting in a single broad lamellipod with static cell-matrix adhesions at the leading edge. Adhesion by alpha 5 beta 1 instead leads to the phosphorylation/inactivation of cofilin, and these cells fail to polarize their cytoskeleton but extend thin protrusions containing highly dynamic cell-matrix adhesions in multiple directions. The activity of the small GTPase RhoA is particularly high in cells adhering by alpha 5 beta 1, and inhibition of Rho signaling causes a switch from a beta 1- to a beta 3-associated mode of migration, whereas increased Rho activity has the opposite effect. Thus, alterations in integrin expression profiles allow cells to modulate several critical aspects of the motile machinery through Rho GTPases.
引用
收藏
页码:515 / 526
页数:12
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