title: Rab7 and Rab27a control two motor protein activities involved in melanosomal transport.
abstract: Melanosomes are lysosome-related organelles that synthesize, store and transport melanin. In epidermal melanocytes, melanosomes mature and are transferred to surrounding keratinocytes, which is essential for skin and coat colour. Mouse coat colour mutants reveal a critical role for the small GTPase Rab27a, which recruits myosin Va through its effector protein melanophilin/Slac2a. Here we have studied how two different Rab GTPases control two motor proteins during subsequent phases in transport of melanosomes. We show that the small GTPase Rab7 mainly associates with early and intermediate stage melanosomes and Rab27a to intermediate and mature melanosomes. Rab27a is found in an active state on mature melanosomes in the tips of the dendrites. The Rab7-Rab7-interacting lysosomal protein-dynein pathway only controls early and intermediate stage melanosomes because the mature melanosomes lack Rab7 and associate with the actin network through Rab27a recruited MyoVa. Thus two Rab proteins regulate two different motor proteins, thereby controlling complementary phases in melanosome biogenesis: Rab7 controls microtubule-mediated transport of early and Rab27a the subsequent actin-dependent transport of mature melanosomes.
authors.affiliation: Department of Tumour Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Jordens
authors.forename: Wendy
authors.initials: W
authors.lastname: Westbroek
authors.forename: Marije
authors.initials: M
authors.lastname: Marsman
authors.forename: Nuno
authors.initials: N
authors.lastname: Rocha
authors.forename: Mieke
authors.initials: M
authors.lastname: Mommaas
authors.forename: Marjan
authors.initials: M
authors.lastname: Huizing
authors.forename: Jo
authors.initials: J
authors.lastname: Lambert
authors.forename: Jean M
authors.initials: JM
authors.lastname: Naeyaert
authors.forename: Jacques
authors.initials: J
authors.lastname: Neefjes
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D020460:Melanosomes / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D010858:Pigmentation / Q000235:genetics; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000075745:rab27 GTP-Binding Proteins; D000090802:rab7 GTP-Binding Proteins
chemical_list: D000075745:rab27 GTP-Binding Proteins; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; C000716465:rab7 GTP-binding proteins, mouse; C066694:RAB27A protein, human; C512962:Rab27a protein, mouse; D020691:rab GTP-Binding Proteins