MyRIP, a novel Rab effector, enables myosin VIIa recruitment to retinal melanosomes.
Defects of the myosin VIIa motor protein cause deafness and retinal anomalies in humans and mice. We report on the identification of a novel myosin-VIIa-interacting protein that we have named MyRIP (myosin-VIIa- and Rab-interacting protein), since it also binds to Rab27A in a GTP-dependent manner. In the retinal pigment epithelium cells, MyRIP, myosin VIIa and Rab27A are associated with melanosomes. In transfected PC12 cells, overexpression of MyRIP was shown to interfere with the myosin VIIa tail localization. We propose that a molecular complex composed of Rab27A, MyRIP and myosin VIIa 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 myosinVIIa-defective mice.
El-Amraoui
Aziz
A
Unité de Génétique des Déficits Sensoriels, CNRS URA 1968, Institut Pasteur, 25 rue du Dr Roux, F-5724 Paris cedex 15, France.
Schonn
Jéan-Sebastien
JS
Küssel-Andermann
Polonca
P
Blanchard
Stéphane
S
Desnos
Claire
C
Henry
Jean-Pierre
JP
Wolfrum
Uwe
U
Darchen
François
F
Petit
Christine
C
D000595:Amino Acid Sequence; D000818:Animals; D004398:Dyneins; D015723:Gene Library; D006801:Humans; D020460:Melanosomes / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008969:Molecular Sequence Data; D000081412:Myosin VIIa; D009218:Myosins / Q000378:metabolism*; D009928:Organ Specificity; D012160:Retina / Q000378:metabolism*; D016415:Sequence Alignment; D020798:Two-Hybrid System Techniques; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000075745:rab27 GTP-Binding Proteins
C000631455:MYO7A protein, human; C000631456:Myo7a protein, mouse; D000081412:Myosin VIIa; D000075745:rab27 GTP-Binding Proteins; C066694:RAB27A protein, human; C512962:Rab27a protein, mouse; D009218:Myosins; D004398:Dyneins; D020691:rab GTP-Binding Proteins