Regulation of Smoothened ubiquitylation and cell surface expression through a Cul4-DDB1-Gβ E3 ubiquitin ligase complex.

ABSTRACT: Hedgehog (Hh) transduces signals by promoting cell surface accumulation and activation of the G-protein-coupled receptor (GPCR)-family protein Smoothened (Smo) in Drosophila, but the molecular mechanism underlying the regulation of Smo trafficking remains poorly understood. Here, we identified the Cul4-DDB1 E3 ubiquitin ligase complex as being essential for Smo ubiquitylation and cell surface clearance. We found that the C-terminal intracellular domain of Smo recruits Cul4-DDB1 through the β subunit of trimeric G protein (Gβ), and that Cul4-DDB1-Gβ promotes the ubiquitylation of both Smo and its binding partner G-protein-coupled-receptor kinase 2 (Gprk2) and induces the internalization and degradation of Smo. Hh dissociates Cul4-DDB1 from Smo by recruiting the catalytic subunit of p

SUBMITTER: Li S 

PROVIDER: S-EPMC6104825 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature