title: Interactions of human Myosin Va isoforms, endogenously expressed in human melanocytes, are tightly regulated by the tail domain.
abstract: Primary human epidermal melanocytes express six endogenous isoforms of the human actin-associated myosin Va motor protein, involved in organelle transport. As isoforms containing exon F are most abundant in melanocytes, we hypothesized that these isoforms probably have a melanocyte-specific function. To uncover the biologic role of the six isoforms we introduced enhanced green fluorescent protein (eGFP)-myosin Va tail constructs in human melanocytes. We found that the medial tail, undergoing alternative splicing, has to be expressed in combination with the globular tail in order to obtain clear colocalization with organelles. Our data show that isoforms lacking exon F but containing exon D are associated with vesicles near the Golgi area. Myosin Va isoforms containing exon F are able to colocalize with and influence melanosome distribution by indirect interaction with rab27a and direct interaction with melanophilin. These results indicate that the myosin Va medial tail domain provides the globular tail domain with organelle-interacting specificity.
authors.affiliation: Department of Dermatology, Ghent University Hospital, B-Gent, Belgium.
authors.forename: Wendy
authors.initials: W
authors.lastname: Westbroek
authors.forename: Jo
authors.initials: J
authors.lastname: Lambert
authors.forename: Philippe
authors.initials: P
authors.lastname: Bahadoran
authors.forename: Roser
authors.initials: R
authors.lastname: Busca
authors.forename: Marie Chantal
authors.initials: MC
authors.lastname: Herteleer
authors.forename: Nico
authors.initials: N
authors.lastname: Smit
authors.forename: Mieke
authors.initials: M
authors.lastname: Mommaas
authors.forename: Robert
authors.initials: R
authors.lastname: Ballotti
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: Naeyaert
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000502:physiology; D002478:Cells, Cultured; D005091:Exons / Q000502:physiology; D006801:Humans; D008544:Melanocytes / Q000201:enzymology*; D020460:Melanosomes / Q000502:physiology; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism*; D024701:Myosin Type V / Q000235:genetics* / Q000378:metabolism*; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary / Q000502:physiology; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000075745:rab27 GTP-Binding Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C492410:MLPH protein, human; D000075745:rab27 GTP-Binding Proteins; C077511:MYO5A protein, human; D024701:Myosin Type V; C066694:RAB27A protein, human; D018995:Myosin Heavy Chains; D020691:rab GTP-Binding Proteins