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Three sorting nexins drive the degradation of apoptotic cells in response to PtdIns(3)P signaling
Apoptotic cells are swiftly engulfed by phagocytes and degraded inside phagosomes. Phagosome maturation requires phosphatidylinositol 3-phosphate [PtdIns(3)P], yet how PtdIns(3)P triggers phagosome maturation remains largely unknown. Through a genome-wide PtdIns(3)P effector screen in the nematode C...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The American Society for Cell Biology
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031466/ https://www.ncbi.nlm.nih.gov/pubmed/21148288 http://dx.doi.org/10.1091/mbc.e10-09-0756 |
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author | Lu, Nan Shen, Qian Mahoney, Timothy R. Liu, Xianghua Zhou, Zheng |
author_facet | Lu, Nan Shen, Qian Mahoney, Timothy R. Liu, Xianghua Zhou, Zheng |
author_sort | Lu, Nan |
collection | PubMed |
description | Apoptotic cells are swiftly engulfed by phagocytes and degraded inside phagosomes. Phagosome maturation requires phosphatidylinositol 3-phosphate [PtdIns(3)P], yet how PtdIns(3)P triggers phagosome maturation remains largely unknown. Through a genome-wide PtdIns(3)P effector screen in the nematode Caenorhabditis elegans, we identified LST-4/SNX9, SNX-1, and SNX-6, three BAR domain-containing sorting nexins, that act in two parallel pathways to drive PtdIns(3)P-mediated degradation of apoptotic cells. We found that these proteins were enriched on phagosomal surfaces through association with PtdIns(3)P and through specific protein–protein interaction, and they promoted the fusion of early endosomes and lysosomes to phagosomes, events essential for phagosome maturation. Specifically, LST-4 interacts with DYN-1 (dynamin), an essential phagosome maturation initiator, to strengthen DYN-1’s association to phagosomal surfaces, and facilitates the maintenance of the RAB-7 GTPase on phagosomal surfaces. Furthermore, both LST-4 and SNX-1 promote the extension of phagosomal tubules to facilitate the docking and fusion of intracellular vesicles. Our findings identify the critical and differential functions of two groups of sorting nexins in phagosome maturation and reveal a signaling cascade initiated by phagocytic receptor CED-1, mediated by PtdIns(3)P, and executed through these sorting nexins to degrade apoptotic cells. |
format | Text |
id | pubmed-3031466 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-30314662011-04-16 Three sorting nexins drive the degradation of apoptotic cells in response to PtdIns(3)P signaling Lu, Nan Shen, Qian Mahoney, Timothy R. Liu, Xianghua Zhou, Zheng Mol Biol Cell Articles Apoptotic cells are swiftly engulfed by phagocytes and degraded inside phagosomes. Phagosome maturation requires phosphatidylinositol 3-phosphate [PtdIns(3)P], yet how PtdIns(3)P triggers phagosome maturation remains largely unknown. Through a genome-wide PtdIns(3)P effector screen in the nematode Caenorhabditis elegans, we identified LST-4/SNX9, SNX-1, and SNX-6, three BAR domain-containing sorting nexins, that act in two parallel pathways to drive PtdIns(3)P-mediated degradation of apoptotic cells. We found that these proteins were enriched on phagosomal surfaces through association with PtdIns(3)P and through specific protein–protein interaction, and they promoted the fusion of early endosomes and lysosomes to phagosomes, events essential for phagosome maturation. Specifically, LST-4 interacts with DYN-1 (dynamin), an essential phagosome maturation initiator, to strengthen DYN-1’s association to phagosomal surfaces, and facilitates the maintenance of the RAB-7 GTPase on phagosomal surfaces. Furthermore, both LST-4 and SNX-1 promote the extension of phagosomal tubules to facilitate the docking and fusion of intracellular vesicles. Our findings identify the critical and differential functions of two groups of sorting nexins in phagosome maturation and reveal a signaling cascade initiated by phagocytic receptor CED-1, mediated by PtdIns(3)P, and executed through these sorting nexins to degrade apoptotic cells. The American Society for Cell Biology 2011-02-01 /pmc/articles/PMC3031466/ /pubmed/21148288 http://dx.doi.org/10.1091/mbc.e10-09-0756 Text en © 2011 Lu et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,“ “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Lu, Nan Shen, Qian Mahoney, Timothy R. Liu, Xianghua Zhou, Zheng Three sorting nexins drive the degradation of apoptotic cells in response to PtdIns(3)P signaling |
title | Three sorting nexins drive the degradation of apoptotic cells in response to PtdIns(3)P signaling |
title_full | Three sorting nexins drive the degradation of apoptotic cells in response to PtdIns(3)P signaling |
title_fullStr | Three sorting nexins drive the degradation of apoptotic cells in response to PtdIns(3)P signaling |
title_full_unstemmed | Three sorting nexins drive the degradation of apoptotic cells in response to PtdIns(3)P signaling |
title_short | Three sorting nexins drive the degradation of apoptotic cells in response to PtdIns(3)P signaling |
title_sort | three sorting nexins drive the degradation of apoptotic cells in response to ptdins(3)p signaling |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031466/ https://www.ncbi.nlm.nih.gov/pubmed/21148288 http://dx.doi.org/10.1091/mbc.e10-09-0756 |
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