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

Autor: Ayaka Yatsu, Hikaru Shimada, Norihiko Ohbayashi, Mitsunori Fukuda
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: Biology Open, Vol 4, Iss 3, Pp 267-275 (2015)
Druh dokumentu: article
ISSN: 2046-6390
DOI: 10.1242/bio.201411114
Popis: 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.
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