論文 - 詳細
| RRC ID | 51381 |
|---|---|
| 著者 | Law F, Seo JH, Wang Z, DeLeon JL, Bolis Y, Brown A, Zong WX, Du G, Rocheleau CE. |
| タイトル | The VPS34 PI3K negatively regulates RAB-5 during endosome maturation. |
| ジャーナル | J Cell Sci |
| Abstract |
The GTPase Rab5 and phosphatidylinositol-3 phosphate [PI(3)P] coordinately regulate endosome trafficking. Rab5 recruits Vps34, the class III phosphoinositide 3-kinase (PI3K), to generate PI(3)P and recruit PI(3)P-binding proteins. Loss of Rab5 and loss of Vps34 have opposite effects on endosome size, suggesting that our understanding of how Rab5 and PI(3)P cooperate is incomplete. Here, we report a novel regulatory loop whereby Caenorhabditis elegans VPS-34 inactivates RAB-5 via recruitment of the TBC-2 Rab GTPase-activating protein. We found that loss of VPS-34 caused a phenotype with large late endosomes, as with loss of TBC-2, and that Rab5 activity (mice have two Rab5 isoforms, Rab5a and Rab5b) is increased in Vps34-knockout mouse embryonic fibroblasts (Vps34 is also known as PIK3C3 in mammals). We found that VPS-34 is required for TBC-2 endosome localization and that the pleckstrin homology (PH) domain of TBC-2 bound PI(3)P. Deletion of the PH domain enhanced TBC-2 localization to endosomes in a VPS-34-dependent manner. Thus, PI(3)P binding of the PH domain might be permissive for another PI(3)P-regulated interaction that recruits TBC-2 to endosomes. Therefore, VPS-34 recruits TBC-2 to endosomes to inactivate RAB-5 to ensure the directionality of endosome maturation. |
| 巻・号 | 130(12) |
| ページ | 2007-2017 |
| 公開日 | 2017-6-15 |
| DOI | 10.1242/jcs.194746 |
| PII | jcs.194746 |
| PMID | 28455411 |
| PMC | PMC5482978 |
| MeSH | Animals Animals, Genetically Modified Caenorhabditis elegans Caenorhabditis elegans Proteins / metabolism* Cell Membrane / metabolism Class III Phosphatidylinositol 3-Kinases / metabolism* Endosomes / metabolism* Fibroblasts / metabolism GTPase-Activating Proteins / metabolism* Green Fluorescent Proteins / metabolism Liposomes / chemistry Mice Mice, Knockout Mutation Phenotype Plasmids / metabolism Protein Domains RNA Interference rab5 GTP-Binding Proteins / metabolism* |
| IF | 4.573 |
| 引用数 | 11 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 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 | |
| 線虫 | tm2241 |