MyRIP, a novel Rab effector, enables myosin VIIa recruitment to retinal melanosomes

Defects of the myosin Vila motor protein cause deafness and retinal anomalies in humans and mice. We report on the identification of a novel myosin-Vila-interacting protein that we have named MyRIP (myosin-Vlla- and Rab-interacting protein), since it also binds to Rab27A in a GTP-dependent manner. In the retinal pigment epithelium cells, MyRIP, myosin Vila and Rab27A are associated with melanosomes. In transfected PC12 cells, overexpression of MyRIP was shown to interfere with the myosin Vila tail localization. We propose that a molecular complex composed of Rab27A, MyRIP and myosin Vila bridges retinal melanosomes to the actin cytoskeleton and thereby mediates the local trafficking of these organelles. The defect of this molecular complex is likely to account for the perinuclear mislocalization of the melanosomes observed in the retinal pigment epithelium cells of myosinVlla-defective mice.