A Varp-Binding Protein, RACK1, Regulates Dendrite Outgrowth through Stabilization of Varp Protein in Mouse Melanocytes

Soujiro Marubashi, Norihiko Ohbayashi, Mitsunori Fukuda

    Research output: Contribution to journalArticle

    9 Citations (Scopus)

    Abstract

    Varp (VPS9-ankyrin repeat protein) in melanocytes is thought to function as a key player in the pigmentation of mammals. Varp regulates two different melanocyte functions: (i) transport of melanogenic enzymes to melanosomes by functioning as a Rab32/38 effector and (ii) promotion of dendrite outgrowth by functioning as a Rab21-guanine nucleotide exchange factor. The Varp protein level has recently been shown to be negatively regulated by proteasomal degradation through interaction of the ankyrin repeat 2 (ANKR2) domain of Varp with Rab40C. However, the molecular mechanisms by which Varp escapes from Rab40C and retains its own expression level remain completely unknown. Here, we identified RACK1 (receptor of activated protein kinase C 1) as a Varp-ANKR2 binding partner and investigated its involvement in Varp stabilization in mouse melanocytes. The results showed that knockdown of endogenous RACK1 in melanocytes caused dramatic reduction of the Varp protein level and inhibition of dendrite outgrowth, and intriguingly, overexpression of RACK1 inhibited the interaction between Varp and Rab40C and counteracted the negative effect of Rab40C on dendrite outgrowth. These findings indicated that RACK1 competes with Rab40C for binding to the ANKR2 domain of Varp and regulates dendrite outgrowth through stabilization of Varp in mouse melanocytes.

    Original languageEnglish
    Pages (from-to)1672-1680
    Number of pages9
    JournalJournal of Investigative Dermatology
    Volume136
    Issue number8
    DOIs
    Publication statusPublished - 2016 Aug 1

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Dermatology
    • Cell Biology

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