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

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 alpha-helix-based coiled-coil structure.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Binding Sites, Biological Transport, Carrier Proteins, Humans, Macromolecular Substances, Melanocytes, Melanoma, Melanosomes, Microfilaments, Molecular Sequence Data, Myosin Type V, Protein Conformation, Sequence Alignment, Tumor Cells, Cultured, rab GTP-Binding Proteins
FEBS Lett.
Date: Apr. 24, 2002
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