論文 - 詳細
| RRC ID | 76169 |
|---|---|
| 著者 | Fazeli G, Levin-Konigsberg R, Bassik MC, Stigloher C, Wehman AM. |
| タイトル | A BORC-dependent molecular pathway for vesiculation of cell corpse phagolysosomes. |
| ジャーナル | Curr Biol |
| Abstract |
Phagocytic clearance is important to provide cells with metabolites and regulate immune responses, but little is known about how phagolysosomes finally resolve their phagocytic cargo of cell corpses, cell debris, and pathogens. While studying the phagocytic clearance of non-apoptotic polar bodies in C. elegans, we previously discovered that phagolysosomes tubulate into small vesicles to facilitate corpse clearance within 1.5 h. Here, we show that phagolysosome vesiculation depends on amino acid export by the solute transporter SLC-36.1 and the activation of TORC1. We demonstrate that downstream of TORC1, BLOC-1-related complex (BORC) is de-repressed by Ragulator through the BORC subunit BLOS-7. In addition, the BORC subunit SAM-4 is needed continuously to recruit the small GTPase ARL-8 to the phagolysosome for tubulation. We find that disrupting the regulated GTP-GDP cycle of ARL-8 reduces tubulation by kinesin-1, delays corpse clearance, and mislocalizes ARL-8 away from lysosomes. We also demonstrate that mammalian phagocytes use BORC to promote phagolysosomal degradation, confirming the conserved importance of TOR and BORC. Finally, we show that HOPS is required after tubulation for the rapid degradation of cargo in small phagolysosomal vesicles, suggesting that additional rounds of lysosome fusion occur. Thus, by observing single phagolysosomes over time, we identified the molecular pathway regulating phagolysosome vesiculation that promotes efficient resolution of phagocytosed cargos. |
| 巻・号 | 33(4) |
| ページ | 607-621.e7 |
| 公開日 | 2023-2-27 |
| DOI | 10.1016/j.cub.2022.12.041 |
| PII | S0960-9822(22)01978-9 |
| PMID | 36652947 |
| PMC | PMC9992095 |
| MeSH | Animals Apoptosis Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Lysosomes / metabolism Mammals Mechanistic Target of Rapamycin Complex 1 / metabolism Multiprotein Complexes Phagocytosis Phagosomes / metabolism |
| 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 | 15 |
| 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 | tm2367 tm3828 tm2504 |