2017 Fiscal Year Final Research Report
Degradation mechanism of effector molecules by Rab small GTPase
| Project/Area Number |
15K07039
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 色素細胞 / Rab / プロテアソーム / メラニン合成酵素 / 低分子量Gタンパク質 |
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| Outline of Final Research Achievements |
Varp has been shown to function as a Rab32/Rab38 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 Rab40C was identified as a novel ANKR2-binding protein and it was investigated that Rab40C-involvement in melanogenic enzyme trafficking in melanocytes. The results here 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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| Free Research Field |
細胞生物学
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