RRC ID 39589
Author Fukuda M, Kuroda TS, Mikoshiba K.
Title Slac2-a/melanophilin, the missing link between Rab27 and myosin Va: implications of a tripartite protein complex for melanosome transport.
Journal J Biol Chem
Abstract Myosin Va is a member of the unconventional class V myosin family, and a mutation in the myosin Va gene causes pigment granule transport defects in human Griscelli syndrome and dilute mice. How myosin Va recognizes its cargo (i.e. melanosomes), however, has remained undetermined over the past decade. In this study, we discovered Slac2-a/melanophilin to be the "missing link" between myosin Va and GTP-Rab27A present in the melanosome. Deletion analysis and site-directed mutagenesis showed that the N-terminal Slp (synaptotagmin-like protein) homology domain of Slac2-a specifically binds Rab27A/B isoforms and that the C-terminal half directly binds the globular tail of myosin Va. The tripartite protein complex (Rab27A.Slac2-a.myosin Va) in melanoma cells was further confirmed by immunoprecipitation. The discovery that myosin Va indirectly recognizes its cargo through Slac2-a, a novel Rab27A/B effector, should shed light on molecular recognition of its specific cargo by class V myosin.
Volume 277(14)
Pages 12432-6
Published 2002-4-5
DOI 10.1074/jbc.C200005200
PII C200005200
PMID 11856727
MeSH Adaptor Proteins, Signal Transducing Animals Brain / metabolism COS Cells Carrier Proteins / chemistry* Carrier Proteins / metabolism* Cloning, Molecular DNA, Complementary / metabolism Gene Deletion Humans Melanosomes / metabolism Mice Models, Biological Mutagenesis, Site-Directed Mutation Myosin Heavy Chains / chemistry Myosin Heavy Chains / metabolism* Myosin Type V / chemistry Myosin Type V / metabolism* Precipitin Tests Protein Binding Protein Isoforms Protein Structure, Tertiary Protein Transport Transfection rab GTP-Binding Proteins / chemistry rab GTP-Binding Proteins / metabolism* rab27 GTP-Binding Proteins
IF 4.238
Times Cited 254
DNA material Slac2-a (RDB03422) pEF-FLAG-mouse myosin Va (Brain type) (RDB15283) pEF-FLAG-mouse Rab34 (RDB15394).