論文 - 詳細
| RRC ID | 4251 |
|---|---|
| 著者 | Kinchen JM, Doukoumetzidis K, Almendinger J, Stergiou L, Tosello-Trampont A, Sifri CD, Hengartner MO, Ravichandran KS. |
| タイトル | A pathway for phagosome maturation during engulfment of apoptotic cells. |
| ジャーナル | Nat Cell Biol |
| Abstract |
Removal of apoptotic cells is critical for the physiological well-being of the organism and defects in corpse removal have been linked to disease states. Genes regulating corpse recognition and internalization have been identified, but few molecules involved in the processing of internalized corpses are known. Through a combination of targeted and unbiased reverse genetic screens in Caenorhabditis elegans, and studies in mammalian cells, we have identified genes required for maturation of apoptotic-cell-containing phagosomes. We have further ordered these candidates, which include the GTPases RAB-5 and RAB-7 and the HOPS complex, into a coherent linear pathway for the maturation of apoptotic cells within phagosomes. In depth analysis of two additional candidate genes, the phosphatidylinositol 3 kinase (PI(3)K) vps-34 (A001762) and dyn-1/dynamin, showed an accumulation of internalized, but undegraded, corpses within abnormal Rab5-negative phagosomes. We ordered these candidates in our pathway, with DYN-1 functioning upstream of VPS-34 in the recruitment and/or retention of RAB-5 to the phagosome. Finally, we have also identified a previously undescribed biochemical complex containing Vps34, dynamin and Rab5(GDP), thus providing a mechanism for Rab5 recruitment to the nascent phagosome. |
| 巻・号 | 10(5) |
| ページ | 556-66 |
| 公開日 | 2008-5-1 |
| DOI | 10.1038/ncb1718 |
| PII | ncb1718 |
| PMID | 18425118 |
| PMC | PMC2851549 |
| MeSH | Animals Animals, Genetically Modified Apoptosis / physiology* Caenorhabditis elegans* / cytology Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Dynamins / genetics Dynamins / metabolism Humans Multiprotein Complexes / genetics Multiprotein Complexes / metabolism Phagocytosis / physiology* Phagosomes / metabolism* Phosphatidylinositol 3-Kinases / genetics Phosphatidylinositol 3-Kinases / metabolism RNA Interference Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism rab GTP-Binding Proteins / genetics rab GTP-Binding Proteins / metabolism* rab5 GTP-Binding Proteins / genetics rab5 GTP-Binding Proteins / metabolism* rab7 GTP-Binding Proteins |
| IF | 20.042 |
| 引用数 | 170 |
| WOS 分野 | CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | F1000Research |
| 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 | tm512 |