Melanophilin directly links Rab27a and myosin Va through its distinct coiled‐coil regions

FEBS Letters

Yi, Zhaohong¹  Okamoto, Koichi⁴  Torii, Seiji²  Izumi, Tetsuro¹  Igarashi, Michihiro³  Takeuchi, Toshiyuki²  Nagashima, Kazuaki¹ 

[1] Laboratory of Gene Engineering, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma 371-8512, Japan;Laboratory of Gene Analysis, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma 371-8512, Japan;Division of Molecular and Cellular Biology, Department of Signal Transduction Research, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan;Department of Neurology, Gunma University School of Medicine, Maebashi, Gunma 371-8511, Japan

关键词: Rab effector;    Rab27a;    Myosin Va;    Melanosome;    Coiled-coil;   

DOI  :  10.1016/S0014-5793(02)02634-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Rab GTPases regulate the membrane transport pathways by recruiting their specific effector proteins. Melanophilin, a putative Rab effector, has recently been identified as a gene that is mutated in leaden mice, in which peripheral localization of melanosomes is impaired in melanocytes. Genetic studies suggest that three coat-color mutation genes, dilute (MyoVa^d ), ashen (Rab27a^ash ), and leaden (Mlph^ln ), act in the same or overlapping pathways. Here we have cloned and characterized a human melanophilin homolog, which belongs to the rabphilin3/granuphilin-like Rab effector family. Cosedimentation assays using recombinant proteins reveal that melanophilin directly binds to Rab27a and myosin Va through its N-terminal and its first C-terminal coiled-coil region, respectively. Moreover, we show that Rab27a, melanophilin, and myosin Va form a ternary complex in the human melanocyte cell line HMV-II. These findings suggest that melanophilin has a role in bridging Rab27a on melanosomes and myosin Va on actin filaments during melanosome transport. We also propose that the Rab-binding region conserved in a novel rabphilin3/granuphilin-like Rab effector family constitutes an α-helix-based coiled-coil structure.

【 授权许可】

Unknown