Syk facilitates phagosome-lysosome fusion by regulating actin-remodeling in complement-mediated phagocytosis

Abstract Effective phagocytosis is crucial for host defense against pathogens. Macrophages entrap pathogens into a phagosome and subsequently acidic lysosomes fuse to the phagosome. Previous studies showed the pivotal role of actin-remodeling mediated by phosphoinositide-related signaling in phagoso...

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Auteurs principaux:	Hiroyuki Tabata, Hiroyuki Morita, Hiroaki Kaji, Kaoru Tohyama, Yumi Tohyama
Format:	article
Langue:	EN
Publié:	Nature Portfolio 2020
Sujets:	Medicine R Science Q
Accès en ligne:	https://doaj.org/article/d5dfff707a7f48d58d3fc7b9c6932ac2
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spelling	oai:doaj.org-article:d5dfff707a7f48d58d3fc7b9c6932ac22021-12-02T13:34:10ZSyk facilitates phagosome-lysosome fusion by regulating actin-remodeling in complement-mediated phagocytosis10.1038/s41598-020-79156-72045-2322https://doaj.org/article/d5dfff707a7f48d58d3fc7b9c6932ac22020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79156-7https://doaj.org/toc/2045-2322Abstract Effective phagocytosis is crucial for host defense against pathogens. Macrophages entrap pathogens into a phagosome and subsequently acidic lysosomes fuse to the phagosome. Previous studies showed the pivotal role of actin-remodeling mediated by phosphoinositide-related signaling in phagosome formation, but the mechanisms of phagosome-lysosome fusion remain unexplored. Here we show that in complement-mediated phagocytosis, phagosome-lysosome fusion requires the disappearance of F-actin structure surrounding the phagosome and a tyrosine kinase Syk plays a key role in this process. Using macrophage-like differentiated HL60 and Syk-knockout (Syk-KO) HL60 cells, we found that Syk-KO cells showed insufficient phagosome acidification caused by impaired fusion with lysosomes and permitted the survival of Candida albicans in complement-mediated phagocytosis. Phagosome tracking analysis showed that during phagosome internalization process, F-actin surrounding phagosomes disappeared in both parental and Syk-KO cells but this structure was reconstructed immediately only in Syk-KO cells. In addition, F-actin-stabilizing agent induced a similar impairment of phagosome-lysosome fusion. Collectively, Syk-derived signaling facilitates phagosome-lysosome fusion by regulating actin-remodeling.Hiroyuki TabataHiroyuki MoritaHiroaki KajiKaoru TohyamaYumi TohyamaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-16 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hiroyuki Tabata Hiroyuki Morita Hiroaki Kaji Kaoru Tohyama Yumi Tohyama Syk facilitates phagosome-lysosome fusion by regulating actin-remodeling in complement-mediated phagocytosis
description	Abstract Effective phagocytosis is crucial for host defense against pathogens. Macrophages entrap pathogens into a phagosome and subsequently acidic lysosomes fuse to the phagosome. Previous studies showed the pivotal role of actin-remodeling mediated by phosphoinositide-related signaling in phagosome formation, but the mechanisms of phagosome-lysosome fusion remain unexplored. Here we show that in complement-mediated phagocytosis, phagosome-lysosome fusion requires the disappearance of F-actin structure surrounding the phagosome and a tyrosine kinase Syk plays a key role in this process. Using macrophage-like differentiated HL60 and Syk-knockout (Syk-KO) HL60 cells, we found that Syk-KO cells showed insufficient phagosome acidification caused by impaired fusion with lysosomes and permitted the survival of Candida albicans in complement-mediated phagocytosis. Phagosome tracking analysis showed that during phagosome internalization process, F-actin surrounding phagosomes disappeared in both parental and Syk-KO cells but this structure was reconstructed immediately only in Syk-KO cells. In addition, F-actin-stabilizing agent induced a similar impairment of phagosome-lysosome fusion. Collectively, Syk-derived signaling facilitates phagosome-lysosome fusion by regulating actin-remodeling.
format	article
author	Hiroyuki Tabata Hiroyuki Morita Hiroaki Kaji Kaoru Tohyama Yumi Tohyama
author_facet	Hiroyuki Tabata Hiroyuki Morita Hiroaki Kaji Kaoru Tohyama Yumi Tohyama
author_sort	Hiroyuki Tabata
title	Syk facilitates phagosome-lysosome fusion by regulating actin-remodeling in complement-mediated phagocytosis
title_short	Syk facilitates phagosome-lysosome fusion by regulating actin-remodeling in complement-mediated phagocytosis
title_full	Syk facilitates phagosome-lysosome fusion by regulating actin-remodeling in complement-mediated phagocytosis
title_fullStr	Syk facilitates phagosome-lysosome fusion by regulating actin-remodeling in complement-mediated phagocytosis
title_full_unstemmed	Syk facilitates phagosome-lysosome fusion by regulating actin-remodeling in complement-mediated phagocytosis
title_sort	syk facilitates phagosome-lysosome fusion by regulating actin-remodeling in complement-mediated phagocytosis
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/d5dfff707a7f48d58d3fc7b9c6932ac2
work_keys_str_mv	AT hiroyukitabata sykfacilitatesphagosomelysosomefusionbyregulatingactinremodelingincomplementmediatedphagocytosis AT hiroyukimorita sykfacilitatesphagosomelysosomefusionbyregulatingactinremodelingincomplementmediatedphagocytosis AT hiroakikaji sykfacilitatesphagosomelysosomefusionbyregulatingactinremodelingincomplementmediatedphagocytosis AT kaorutohyama sykfacilitatesphagosomelysosomefusionbyregulatingactinremodelingincomplementmediatedphagocytosis AT yumitohyama sykfacilitatesphagosomelysosomefusionbyregulatingactinremodelingincomplementmediatedphagocytosis
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Syk facilitates phagosome-lysosome fusion by regulating actin-remodeling in complement-mediated phagocytosis

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