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

Ayaka Yatsu, Hikaru Shimada, Norihiko Ohbayashi, Mitsunori Fukuda

    Research output: Contribution to journalArticle

    13 Citations (Scopus)

    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 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.

    Original languageEnglish
    Pages (from-to)267-275
    Number of pages9
    JournalBiology Open
    Volume4
    Issue number3
    DOIs
    Publication statusPublished - 2015 Mar 15

    Keywords

    • Degradation
    • Melanogenic enzyme
    • Membrane traffic
    • Rab40C
    • Varp

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Agricultural and Biological Sciences(all)

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