論文 - 詳細
| RRC ID | 64980 |
|---|---|
| 著者 | Higashio H, Satoh Y, Saino T. |
| タイトル | Mast cell degranulation is negatively regulated by the Munc13-4-binding small-guanosine triphosphatase Rab37. |
| ジャーナル | Sci Rep |
| Abstract |
Mast cell degranulation is regulated by the small guanosine triphosphatases (GTPases) Rab27a and Rab27b, which have distinct and opposing roles: Rab27b acts as a positive regulator through its effector protein Munc13-4, a non-neuronal isoform of the vesicle-priming Munc13 family of proteins, whereas Rab27a acts as a negative regulator through its effector protein melanophilin, by maintaining integrity of cortical filamentous actin (F-actin), a barrier to degranulation. Here we investigated the role of Rab37, one of the Rab GTPases assumed to be implicated in regulated secretion during mast cell degranulation. Using the RBL-2H3 mast cell line, we detected Rab37 on the secretory granules and found that antigen-induced degranulation was extensively increased by either knockdown of Rab37 or overexpression of a dominant-active Rab37 mutant. This hypersecretion phenotype in the Rab37-knockdown cells was suppressed by simultaneous knockdown of Rab27a and Rab27b or of Munc13-4, but not by disruption of cortical F-actin. We further found that Rab37 interacted with Munc13-4 in a GTP-independent manner and formed a Rab27-Munc13-4-Rab37 complex. These results suggest that Rab37 is a Munc13-4-binding protein that inhibits mast cell degranulation through its effector protein, by counteracting the vesicle-priming activity of the Rab27-Munc13-4 system. |
| 巻・号 | 6 |
| ページ | 22539 |
| 公開日 | 2016-3-2 |
| DOI | 10.1038/srep22539 |
| PII | srep22539 |
| PMID | 26931073 |
| PMC | PMC4773767 |
| MeSH | Animals Cell Degranulation* Cell Line Mast Cells / cytology* Proteins / metabolism* Rats rab GTP-Binding Proteins / genetics rab GTP-Binding Proteins / physiology* |
| IF | 3.998 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | COS-7(RCB0539) |