RRC ID |
39589
|
著者 |
Fukuda M, Kuroda TS, Mikoshiba K.
|
タイトル |
Slac2-a/melanophilin, the missing link between Rab27 and myosin Va: implications of a tripartite protein complex for melanosome transport.
|
ジャーナル |
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.
|
巻・号 |
277(14)
|
ページ |
12432-6
|
公開日 |
2002-4-5
|
DOI |
10.1074/jbc.C200005200
|
PII |
S0021-9258(18)52075-5
|
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
|
引用数 |
254
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
遺伝子材料 |
Slac2-a (RDB03422)
pEF-FLAG-mouse myosin Va (Brain type) (RDB15283)
pEF-FLAG-mouse Rab34 (RDB15394)
pEF-T7-GST (RDB19882) |