title: 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 beta-catenin whereas C3G interaction with E-cadherin did not involve beta-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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine and Walther Oncology Center, Indianapolis, Indiana 46202, USA.
authors.forename: Sirisha
authors.initials: S
authors.lastname: Asuri
authors.forename: Jingliang
authors.initials: J
authors.lastname: Yan
authors.forename: Nivanka C
authors.initials: NC
authors.lastname: Paranavitana
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Quilliam