| RRC ID |
49210
|
| 著者 |
Ishida M, Arai SP, Ohbayashi N, Fukuda M.
|
| タイトル |
The GTPase-deficient Rab27A(Q78L) mutant inhibits melanosome transport in melanocytes through trapping of Rab27A effector protein Slac2-a/melanophilin in their cytosol: development of a novel melanosome-targetinG tag.
|
| ジャーナル |
J Biol Chem
|
| Abstract |
The small GTPase Rab27A is a crucial regulator of actin-based melanosome transport in melanocytes, and functionally defective Rab27A causes human Griscelli syndrome type 2, which is characterized by silvery hair. A GTPase-deficient, constitutively active Rab27A(Q78L) mutant has been shown to act as an inhibitor of melanosome transport and to induce perinuclear aggregation of melanosomes, but the molecular mechanism by which Rab27A(Q78L) inhibits melanosome transport remained to be determined. In this study, we attempted to identify the primary cause of the perinuclear melanosome aggregation induced by Rab27A(Q78L). The results showed that Rab27A(Q78L) is unable to localize on mature melanosomes and that its inhibitory activity on melanosome transport is completely dependent on its binding to the Rab27A effector Slac2-a/melanophilin. When we forcibly expressed Rab27A(Q78L) on mature melanosomes by using a novel melanosome-targeting tag that we developed in this study and named the MST tag, the MST-Rab27A(Q78L) fusion protein behaved in the same manner as wild-type Rab27A. It localized on mature melanosomes without inducing melanosome aggregation and restored normal peripheral melanosome distribution in Rab27A-deficient cells. These findings indicate that the GTPase activity of Rab27A is required for its melanosome localization but is not required for melanosome transport.
|
| 巻・号 |
289(16)
|
| ページ |
11059-11067
|
| 公開日 |
2014-4-18
|
| DOI |
10.1074/jbc.M114.552281
|
| PII |
S0021-9258(20)48325-5
|
| PMID |
24584932
|
| PMC |
PMC4036246
|
| MeSH |
Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism*
Amino Acid Substitution
Animals
COS Cells
Chlorocebus aethiops
Humans
Immunologic Deficiency Syndromes / genetics
Immunologic Deficiency Syndromes / metabolism
Immunologic Deficiency Syndromes / pathology
Lymphohistiocytosis, Hemophagocytic
Melanosomes / genetics
Melanosomes / metabolism*
Melanosomes / pathology
Mice
Mutation, Missense*
Piebaldism / genetics
Piebaldism / metabolism
Piebaldism / pathology
Primary Immunodeficiency Diseases
Protein Transport / genetics
rab GTP-Binding Proteins / genetics
rab GTP-Binding Proteins / metabolism*
rab27 GTP-Binding Proteins
|
| IF |
4.238
|
| 引用数 |
6
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| 遺伝子材料 |
pCMV-Mreg delta C/MST-mStr(RDB15184)
pCMV-Mreg delta C/MST-mStr-Rab27A-QL/CA (RDB15185)
pmStr-N1-Mreg (RDB15183). |
