TY - JOUR
T1 - Integrins control motile strategy through a Rho-cofilin pathway
AU - Danen, Erik H. J.
AU - van Rheenen, Jacco
AU - Franken, Willeke
AU - Huveneers, Stephan
AU - Sonneveld, Petra
AU - Jalink, Kees
AU - Sonnenberg, Arnoud
PY - 2005
Y1 - 2005
N2 - During wound healing, angiogenesis, and tumor invasion, cells often change their expression profiles of fibronectin- binding integrins. Here, we show that β 1 integrins promote random migration, whereas β 3 integrins promote persistent migration in the same epithelial cell background. Adhesion to fibronectin by α vβ 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 α 5β 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 α 5β 1, and inhibition of Rho signaling causes a switch from a β 1- to a β 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
AB - During wound healing, angiogenesis, and tumor invasion, cells often change their expression profiles of fibronectin- binding integrins. Here, we show that β 1 integrins promote random migration, whereas β 3 integrins promote persistent migration in the same epithelial cell background. Adhesion to fibronectin by α vβ 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 α 5β 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 α 5β 1, and inhibition of Rho signaling causes a switch from a β 1- to a β 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
U2 - https://doi.org/10.1083/jcb.200412081
DO - https://doi.org/10.1083/jcb.200412081
M3 - Article
C2 - 15866889
SN - 0021-9525
VL - 169
SP - 515
EP - 526
JO - Journal of cell biology
JF - Journal of cell biology
IS - 3
ER -