論文 - 詳細
| RRC ID | 53270 |
|---|---|
| 著者 | Topalidou I, Cattin-Ortolá J, Pappas AL, Cooper K, Merrihew GE, MacCoss MJ, Ailion M. |
| タイトル | The EARP Complex and Its Interactor EIPR-1 Are Required for Cargo Sorting to Dense-Core Vesicles. |
| ジャーナル | PLoS Genet |
| Abstract |
The dense-core vesicle is a secretory organelle that mediates the regulated release of peptide hormones, growth factors, and biogenic amines. Dense-core vesicles originate from the trans-Golgi of neurons and neuroendocrine cells, but it is unclear how this specialized organelle is formed and acquires its specific cargos. To identify proteins that act in dense-core vesicle biogenesis, we performed a forward genetic screen in Caenorhabditis elegans for mutants defective in dense-core vesicle function. We previously reported the identification of two conserved proteins that interact with the small GTPase RAB-2 to control normal dense-core vesicle cargo-sorting. Here we identify several additional conserved factors important for dense-core vesicle cargo sorting: the WD40 domain protein EIPR-1 and the endosome-associated recycling protein (EARP) complex. By assaying behavior and the trafficking of dense-core vesicle cargos, we show that mutants that lack EIPR-1 or EARP have defects in dense-core vesicle cargo-sorting similar to those of mutants in the RAB-2 pathway. Genetic epistasis data indicate that RAB-2, EIPR-1 and EARP function in a common pathway. In addition, using a proteomic approach in rat insulinoma cells, we show that EIPR-1 physically interacts with the EARP complex. Our data suggest that EIPR-1 is a new interactor of the EARP complex and that dense-core vesicle cargo sorting depends on the EARP-dependent trafficking of cargo through an endosomal sorting compartment. |
| 巻・号 | 12(5) |
| ページ | e1006074 |
| 公開日 | 2016-5-1 |
| DOI | 10.1371/journal.pgen.1006074 |
| PII | PGENETICS-D-16-00512 |
| PMID | 27191843 |
| PMC | PMC4871572 |
| MeSH | Animals Biogenic Amines / metabolism Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics* Carrier Proteins / genetics* Endosomes / genetics Endosomes / metabolism Golgi Apparatus / genetics Golgi Apparatus / metabolism Intercellular Signaling Peptides and Proteins / genetics Multiprotein Complexes / genetics Mutation Neurons / metabolism Peptide Hormones / genetics Proteomics Secretory Vesicles / genetics* Secretory Vesicles / metabolism Synaptic Vesicles / genetics* Synaptic Vesicles / metabolism rab2 GTP-Binding Protein / genetics* rab2 GTP-Binding Protein / metabolism |
| IF | 5.175 |
| 引用数 | 16 |
| 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 | 3 |
| 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 | tm3622 tm4275 tm4790 |