Melanophilin

Melanophilin is a member of the exophilin subfamily of Rab effector proteins that is encoded by the MLPH gene . The protein forms a ternary complex with the small Ras-related GTPase Rab27A in its GTP-bound form and the motor protein MYO5A . A similar protein complex in the mouse has the function of binding melanosomes to the actin cytoskeleton in melanocytes and is required for visible pigmentation in hair and skin.

Melanophilin plays a crucial role in the regulation of skin pigmentation through the melanosome transport process. The expression of Mlph is regulated by the glucocorticoid receptor (GR). Alteration of GR activity by a specific GR agonist or antagonist only regulated the expression of Mlph among the three major melanosome transport proteins.

Melanosomes are transported by kinesin, dynein and myosin motors. Therefore, melanosome transport is ideally suited to study the functional relationship between the microtubule and actin-based transport systems. In mammalian melanocytes, the Rab27a/melanophilin/myosin-Va complex is known to mediate actin-based transport in vivo. Melanophilin, in particular its C-terminal actin-binding domain (ABD), plays a major role in the pathways that regulate the overall directionality of melanosomes on the actin/microtubule networks. Dephosphorylated melanophilin binds preferentially to microtubules even in the presence of actin, whereas phosphorylated melanophilin associates with actin. In the simultaneous presence of actin and microtubules, the phosphorylation state of melanophilin led to the activation of the Rab27a/melanophilin/myosin-Va transport complex.

A mutation in this gene leads to Griscelli syndrome type 3, which is characterized, among other things, by a silver-grey hair color and abnormal pigment distribution in the hair shaft.

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