E‐cadherin dis‐engagement activates the Rap1 GTPase

Abstract

E‐cadherin based adherens junctions are finely regulated by multiple cellular signaling events. Here we show that the Ras‐related Rap1 GTPase is enriched in regions of nascent cell–cell contacts and strengthens E‐cadherin junctions: constitutively active Rap1 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‐GEF I. PDZ‐GEF I associated with E‐cadherin and β‐catenin whereas C3G interaction with E‐cadherin did not involve β‐catenin. Knockdown of PDZ‐GEF I in MDCK cells decreased Rap1 activity following E‐cadherin junction disruption. We hereby show that Rap1 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‐GEF I. J. Cell. Biochem. 105: 1027–1037, 2008.