Rab27Amelanophilinmyosin

Rab27a melanophilin, also described as the Rab27a–melanophilin complex, refers to the interaction between the small GTPase Rab27a and its effector melanophilin (Mlph) that anchors the motor protein myosin Va to melanosomes in melanocytes. This tripartite complex promotes peripheral transport of melanosomes along actin filaments and is essential for even pigment distribution in skin and hair.

In the active GTP-bound state, Rab27a localizes to melanosome membranes; Mlph binds Rab27a via its Rab27a-binding domain; the C-terminal domain of Mlph binds myosin Va, forming a motor complex that moves melanosomes toward the cell periphery. Regulation occurs through nucleotide cycling, phosphorylation, and interactions with other regulatory factors, enabling controlled clustering or dispersion of melanosomes as needed.

Genetic defects in this pathway manifest as pigmentary disorders. Mutations in RAB27A (Griscelli syndrome type 2) disrupt Rab27a function; mutations in MLPH (Griscelli syndrome type 3) impair Mlph-mediated recruitment of myosin Va; disruptions of MYO5A (Griscelli syndrome type 1) involve myosin Va directly. Collectively, these defects cause hypopigmentation and abnormal melanosome distribution, with varying additional clinical features depending on the affected component.

Beyond pigment cells, Rab27a engages multiple effectors in secretory processes, illustrating the versatility of Rab27a in vesicle trafficking and the broader role of this pathway in cells.