title: Myosin vc interacts with Rab32 and Rab38 proteins and works in the biogenesis and secretion of melanosomes.
abstract: Class V myosins are actin-based motors with conserved functions in vesicle and organelle trafficking. Herein we report the discovery of a function for Myosin Vc in melanosome biogenesis as an effector of melanosome-associated Rab GTPases. We isolated Myosin Vc in a yeast two-hybrid screening for proteins that interact with Rab38, a Rab protein involved in the biogenesis of melanosomes and other lysosome-related organelles. Rab38 and its close homolog Rab32 bind to Myosin Vc but not to Myosin Va or Myosin Vb. Binding depends on residues in the switch II region of Rab32 and Rab38 and regions of the Myosin Vc coiled-coil tail domain. Myosin Vc also interacts with Rab7a and Rab8a but not with Rab11, Rab17, and Rab27. Although Myosin Vc is not particularly abundant on pigmented melanosomes, its knockdown in MNT-1 melanocytes caused defects in the trafficking of integral membrane proteins to melanosomes with substantially increased surface expression of Tyrp1, nearly complete loss of Tyrp2, and significant Vamp7 mislocalization. Knockdown of Myosin Vc in MNT-1 cells more than doubled the abundance of pigmented melanosomes but did not change the number of unpigmented melanosomes. Together the data demonstrate a novel role for Myosin Vc in melanosome biogenesis and secretion.
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523, the Department of Chemistry and Biochemistry, University of Colorado, Colorado Springs, Colorado Springs, Colorado 80918.
authors.forename: Jarred J
authors.initials: JJ
authors.lastname: Bultema
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Boyle
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523.
authors.forename: Parker B
authors.initials: PB
authors.lastname: Malenke
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523.
authors.forename: Faye E
authors.initials: FE
authors.lastname: Martin
authors.affiliation: the Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, California 90095, and.
authors.forename: Esteban C
authors.initials: EC
authors.lastname: Dell'Angelica
authors.affiliation: the Department of Cell Biology and Physiology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Cheney
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523, santiago.dipietro@colostate.edu.
authors.forename: Santiago M
authors.initials: SM
authors.lastname: Di Pietro
mesh_terms: D002460:Cell Line; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism*; D020460:Melanosomes / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D024701:Myosin Type V / Q000235:genetics / Q000378:metabolism*; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C459104:MYO5C protein, human; D008562:Membrane Glycoproteins; D010088:Oxidoreductases; C489799:TYRP1 protein, human; D024701:Myosin Type V; C412058:RAB38 protein, human; C466094:Rab32 protein, human; D020691:rab GTP-Binding Proteins; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase
keywords: Melanogenesis; Membrane Protein; Membrane Trafficking; Myosin; Organelle; Protein Sorting; Rab