title: MyRIP, a novel Rab effector, enables myosin VIIa recruitment to retinal melanosomes.
abstract: 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.
authors.affiliation: Unité de Génétique des Déficits Sensoriels, CNRS URA 1968, Institut Pasteur, 25 rue du Dr Roux, F-5724 Paris cedex 15, France.
authors.forename: Aziz
authors.initials: A
authors.lastname: El-Amraoui
authors.forename: Jéan-Sebastien
authors.initials: JS
authors.lastname: Schonn
authors.forename: Polonca
authors.initials: P
authors.lastname: Küssel-Andermann
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanchard
authors.forename: Claire
authors.initials: C
authors.lastname: Desnos
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Henry
authors.forename: Uwe
authors.initials: U
authors.lastname: Wolfrum
authors.forename: François
authors.initials: F
authors.lastname: Darchen
authors.forename: Christine
authors.initials: C
authors.lastname: Petit
mesh_terms: 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
chemical_list: 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