The scaffold protein Ajuba suppresses CdGAP activity in epithelia to maintain stable cell-cell contacts.

摘要: Levels of active Rac1 at epithelial junctions are partially modulated via interaction with Ajuba, an actin binding and scaffolding protein. Here we demonstrate that Ajuba interacts the Cdc42 GTPase activating protein CdGAP, a GAP for Cdc42, cell-cell contacts. CdGAP recruitment to does not require Ajuba; rather seems control residence sites adhesion. expression potently perturbs inhibits activity. distinct domains can potentially bring them in close proximity facilitate activity regulation. Functionally, CdGAP-Ajuba maintains junctional integrity homeostasis diseases: (i) gain-of-function mutants found Adams-Oliver Syndrome patients strongly destabilize contacts (ii) mRNA levels inversely correlated E-cadherin different cancers. We present conceptual insights on how integrate inactivation spatio-temporal regulation junctions. provides novel mechanism due its ability bind influence activation status both proteins. This functional interplay may contribute towards conserving tissue architecture steady-state pathologies.