Rap1 and its effector KRIT1/CCM1 regulate beta-catenin signaling.

ABSTRACT: KRIT1, also called CCM1, is a member of a multiprotein complex that contains the products of the CCM2 and PDCD10 (also known as CCM3) loci. Heterozygous loss of any of the genes that encode these proteins leads to cerebral cavernous malformations (CCM), which are vascular lesions that are found in around 0.5% of humans. KRIT1 mediates the stabilization of beta-catenin-containing endothelial cell-cell junctions downstream of the Rap1 GTPase. Here, we report that Rap1 and KRIT1 are negative regulators of canonical beta-catenin signaling in mice and that hemizygous Krit1 deficiency exacerbates beta-catenin-driven pathologies. Depletion of endothelial KRIT1 caused beta-catenin to dissociate from vascular endothelial (VE)-cadherin and to accumulate in the nucleus with consequent increases in be

SUBMITTER: Glading AJ 

PROVIDER: S-EPMC2806902 | biostudies-literature | 2010 Jan-Feb

REPOSITORIES: biostudies-literature