論文 - 詳細
| RRC ID | 46351 |
|---|---|
| 著者 | Hannemann M, Sasidharan N, Hegermann J, Kutscher LM, Koenig S, Eimer S. |
| タイトル | TBC-8, a putative RAB-2 GAP, regulates dense core vesicle maturation in Caenorhabditis elegans. |
| ジャーナル | PLoS Genet |
| Abstract |
Dense core vesicles (DCVs) are thought to be generated at the late Golgi apparatus as immature DCVs, which subsequently undergo a maturation process through clathrin-mediated membrane remodeling events. This maturation process is required for efficient processing of neuropeptides within DCVs and for removal of factors that would otherwise interfere with DCV release. Previously, we have shown that the GTPase, RAB-2, and its effector, RIC-19, are involved in DCV maturation in Caenorhabditis elegans motoneurons. In rab-2 mutants, specific cargo is lost from maturing DCVs and missorted into the endosomal/lysosomal degradation route. Cargo loss could be prevented by blocking endosomal delivery. This suggests that RAB-2 is involved in retention of DCV components during the sorting process at the Golgi-endosomal interface. To understand how RAB-2 activity is regulated at the Golgi, we screened for RAB-2-specific GTPase activating proteins (GAPs). We identified a potential RAB-2 GAP, TBC-8, which is exclusively expressed in neurons and which, when depleted, shows similar DCV maturation defects as rab-2 mutants. We could demonstrate that RAB-2 binds to its putative GAP, TBC-8. Interestingly, TBC-8 also binds to the RAB-2 effector, RIC-19. This interaction appears to be conserved as TBC-8 also interacted with the human ortholog of RIC-19, ICA69. Therefore, we propose that a dynamic ON/OFF cycling of RAB-2 at the Golgi induced by the GAP/effector complex is required for proper DCV maturation. |
| 巻・号 | 8(5) |
| ページ | e1002722 |
| 公開日 | 2012-1-1 |
| DOI | 10.1371/journal.pgen.1002722 |
| PII | PGENETICS-D-11-02278 |
| PMID | 22654674 |
| PMC | PMC3359978 |
| MeSH | Animals Autoantigens / metabolism Caenorhabditis elegans* / genetics Caenorhabditis elegans* / growth & development Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Clathrin-Coated Vesicles / genetics Clathrin-Coated Vesicles / physiology Endosomes / genetics Endosomes / metabolism GTPase-Activating Proteins / genetics GTPase-Activating Proteins / metabolism* Gene Expression Regulation Golgi Apparatus* / genetics Golgi Apparatus* / metabolism Humans Motor Neurons / metabolism Protein Transport / genetics Secretory Vesicles* / genetics Secretory Vesicles* / physiology rab2 GTP-Binding Protein / genetics* rab2 GTP-Binding Protein / metabolism rab3 GTP-Binding Proteins / genetics rab3 GTP-Binding Proteins / metabolism |
| IF | 5.175 |
| 引用数 | 13 |
| WOS 分野 | GENETICS & HEREDITY |
| 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 | |
| 各媒体での言及数の合計 | 1 |
| 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 | tm3802 tm2282 tm3255 |