Rab40C is a novel Varp-binding protein that promotes proteasomal degradation of Varp in melanocytes.

ABSTRACT: Varp (VPS9-ankyrin repeat protein) was originally identified as an activator of small GTPase Rab21 through its VPS9 domain, but it has subsequently been shown to function as a Rab32/38 effector through its first ANKR1 domain. Although these functions of Varp are important for melanogenesis, Varp contains a second ANKR2 domain, whose function remained completely unknown. Here we identified Rab40C, an atypical Rab containing a SOCS box that recruits a ubiquitin ligase complex, as a novel ANKR2-binding protein and investigated its involvement in melanogenic enzyme trafficking in melanocytes. The results showed that overexpression of Rab40C in melanocytes caused a dramatic reduction in melanogenic enzyme Tyrp1 signals by promoting proteasomal degradation of Varp in a SOCS-box-dependent manner

SUBMITTER: Yatsu A 

PROVIDER: S-EPMC4359733 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature