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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...

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Detalles Bibliográficos
Autores principales: Lu, Nan, Shen, Qian, Mahoney, Timothy R., Liu, Xianghua, Zhou, Zheng
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
Materias:
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.
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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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