CdGAP regulates cell migration and adhesion dynamics in two-and three-dimensional matrix environments.
CdGAP is a Rac1/Cdc42 specific GTPase activating protein (GAP) that localizes to cell-matrix adhesions through an interaction with the adhesion scaffold α-parvin/actopaxin to regulate lamellipodia formation and cell spreading. Herein, we demonstrate, using a combination of siRNA-mediated silencing and overexpression, that cdGAP negatively regulates directed and random migration by controlling adhesion maturation and dynamics through the regulation of both adhesion assembly and disassembly. Interestingly, cdGAP was also localized to adhesions formed in three-dimensional (3D) matrix environments and cdGAP depletion promoted cancer cell migration and invasion through 3D matrices. These findings highlight the importance of GAP proteins in the regulation of Rho family GTPases and the coordination of the cell migration machinery..
Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, New York 13210, USA.
Duncan
D
Wormer
Nicholas O
NO
Deakin
Christopher E
CE
Turner
D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics
C514543:ARHGAP31 protein, human; D020690:GTPase-Activating Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering