| First Author | Yatsu A | Year | 2015 |
| Journal | Biol Open | Volume | 4 |
| Issue | 3 | Pages | 267-75 |
| PubMed ID | 25661869 | Mgi Jnum | J:220987 |
| Mgi Id | MGI:5637622 | Doi | 10.1242/bio.201411114 |
| Citation | Yatsu A, et al. (2015) Rab40C is a novel Varp-binding protein that promotes proteasomal degradation of Varp in melanocytes. Biol Open 4(3):267-75 |
| abstractText | 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 and that knockdown of Rab40C in melanocytes caused an increase in the amount of Varp. Intriguingly, Rab40C knockdown also caused a dramatic reduction in Tyrp1 signals, the same as Varp overexpression did. These findings indicated that Rab40C is a previously unexpected regulator of Tyrp1 trafficking in melanocytes through controlling the proteasomal degradation of Varp. |
