TY - JOUR
T1 - Slac2-a/melanophilin, the missing link between Rab27 and myosin Va
T2 - Implications of a tripartite protein complex for melanosome transport
AU - Fukuda, Mitsunori
AU - Kuroda, Taruho S.
AU - Mikoshiba, Katsuhiko
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002/4/5
Y1 - 2002/4/5
N2 - 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 Sip Slp (synaptotagmin-like protein) homology domain of Slac2-a specifically binds Rab27AfB Rab27AIB isoforms and that the C-terminal half directly binds the globular tail of myosin Va. The tripartite protein complex (Rab27A.-Slac2-a.myosin 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.
AB - 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 Sip Slp (synaptotagmin-like protein) homology domain of Slac2-a specifically binds Rab27AfB Rab27AIB isoforms and that the C-terminal half directly binds the globular tail of myosin Va. The tripartite protein complex (Rab27A.-Slac2-a.myosin 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.
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U2 - 10.1074/jbc.C200005200
DO - 10.1074/jbc.C200005200
M3 - Article
C2 - 11856727
AN - SCOPUS:0037023745
VL - 277
SP - 12432
EP - 12436
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 14
ER -