E-Cadherin Dis-Engagement Activates the Rap1 GTPase

E-cadherin based adherens junctions are finely regulated by multiple cellular signaling events. Here we show that the Ras-related Rap I GTPase is enriched in regions of nascent cell-cell contacts and strengthens E-cadherin junctions: constitutively active Rap I expressing MDCK cells exhibit increased junctional contact and resisted calcium depletion-induced cell-cell junction disruption. E-cadherin disengagement activated Rap1 and this correlated with E-cadherin association with the Rap GEFs, C3G and PDZ-GEFI. PDZ-GEFI associated with E-cadherin and beta-catenin whereas C3G interaction with E-cadherin did not involve P-catenin. Knockdown of PDZ-GEFI in MDCK cells decreased Rap I activity following E-cadherin junction disruption. We hereby show that Rap I plays a role in the maintenance and repair of E-cadherin junctions and is activated via an outside-in signaling pathway initiated by E-cadherin and mediated at least in part by PDZ-GEFI. J. Cell. Biochem. 105: 1027-1037, 2008. (C) 2008 Wiley-Liss, Inc.