Autor: |
Ayaka Yatsu, Hikaru Shimada, Norihiko Ohbayashi, Mitsunori Fukuda |
Jazyk: |
angličtina |
Rok vydání: |
2015 |
Předmět: |
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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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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