論文 - 詳細
| RRC ID | 46364 |
|---|---|
| 著者 | Hsieh HH, Hsu TY, Jiang HS, Wu YC. |
| タイトル | Integrin α PAT-2/CDC-42 signaling is required for muscle-mediated clearance of apoptotic cells in Caenorhabditis elegans. |
| ジャーナル | PLoS Genet |
| Abstract |
Clearance of apoptotic cells by engulfment plays an important role in the homeostasis and development of multicellular organisms. Despite the fact that the recognition of apoptotic cells by engulfment receptors is critical in inducing the engulfment process, the molecular mechanisms are still poorly understood. Here, we characterize a novel cell corpse engulfment pathway mediated by the integrin α subunit PAT-2 in Caenorhabditis elegans and show that it specifically functions in muscle-mediated engulfment during embryogenesis. Inactivation of pat-2 results in a defect in apoptotic cell internalization. The PAT-2 extracellular region binds to the surface of apoptotic cells in vivo, and the intracellular region may mediate signaling for engulfment. We identify essential roles of small GTPase CDC-42 and its activator UIG-1, a guanine-nucleotide exchange factor, in PAT-2-mediated cell corpse removal. PAT-2 and CDC-42 both function in muscle cells for apoptotic cell removal and are co-localized in growing muscle pseudopods around apoptotic cells. Our data suggest that PAT-2 functions through UIG-1 for CDC-42 activation, which in turn leads to cytoskeletal rearrangement and apoptotic cell internalization by muscle cells. Moreover, in contrast to PAT-2, the other integrin α subunit INA-1 and the engulfment receptor CED-1, which signal through the conserved signaling molecules CED-5 (DOCK180)/CED-12 (ELMO) or CED-6 (GULP) respectively, preferentially act in epithelial cells to mediate cell corpse removal during mid-embryogenesis. Our results show that different engulfing cells utilize distinct repertoires of receptors for engulfment at the whole organism level. |
| 巻・号 | 8(5) |
| ページ | e1002663 |
| 公開日 | 2012-1-1 |
| DOI | 10.1371/journal.pgen.1002663 |
| PII | PGENETICS-D-11-02336 |
| PMID | 22615577 |
| PMC | PMC3355063 |
| MeSH | Animals Apoptosis Apoptosis Regulatory Proteins Benzeneacetamides* / metabolism Caenorhabditis elegans* / embryology Caenorhabditis elegans* / genetics Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Carrier Proteins / metabolism Cell Cycle Proteins* / genetics Cell Cycle Proteins* / metabolism Cytoskeletal Proteins / metabolism Cytoskeleton / genetics Cytoskeleton / metabolism Embryonic Development* Eptifibatide GTP-Binding Proteins* / genetics GTP-Binding Proteins* / metabolism Guanine Nucleotide Exchange Factors / metabolism Integrins / metabolism Membrane Proteins / metabolism Muscle, Skeletal / embryology* Peptides / genetics Peptides / metabolism Phosphoproteins / metabolism Pyridines* / metabolism Signal Transduction |
| IF | 5.175 |
| 引用数 | 23 |
| 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 | 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 | tm597 |