Rho family small GTPases are essential for the formation of adherens junctions (AJs) of epithelial cells. We found FilGAP, a Rac specific Rho GTPase-activating protein, promotes the formation of AJs of Madin-Darby canine kidney (MDCK) cells. Knockdown of FilGAP by siRNA stimulated the disassembly and migration of MDCK cells induced by Hepatocyte-growth factor (HGF). Conversely, forced expression of FilGAP induced accumulation of E-cadherin at AJs. Endogenous FilGAP co-localized with E-cadherin at AJs and depletion of FilGAP reduced the amount of E-cadherin expressed at the surface. The Rac GAP domain of FilGAP is necessary for suppression of cell scattering induced by HGF. In agreement with this, knockdown of both Rac1 and FilGAP by their specific siRNAs suppressed cell scattering induced by HGF. Forced expression of Rho kinase (ROCK) induced accumulation of E-cadherin at AJ and depletion of FilGAP prevented the accumulation of E-cadherin. Moreover, wild-type FilGAP but not non-phophorylatable FilGAP mutant rescued the accumulation of E-cadherin at AJs. These results suggest that FilGAP may regulate cell-cell adhesion through inactivation of Rac downstream of Rho/ROCK-signaling in MDCK cells.
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