Exophagy of annexin A2 via RAB11, RAB8A and RAB27A in IFN-γ-stimulated lung epithelial cells

Abstract Annexin A2 (ANXA2), a phospholipid-binding protein, has multiple biological functions depending on its cellular localization. We previously demonstrated that IFN-γ-triggered ANXA2 secretion is associated with exosomal release. Here, we show that IFN-γ-induced autophagy is essential for the...

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Autores principales:	Ying-Da Chen, Yi-Ting Fang, Yi-Lin Cheng, Chiou-Feng Lin, Li-Jin Hsu, Shu-Ying Wang, Robert Anderson, Chih-Peng Chang, Yee-Shin Lin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bc911b52e59b49cab717a6b1e9b33d46
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spelling	oai:doaj.org-article:bc911b52e59b49cab717a6b1e9b33d462021-12-02T16:06:02ZExophagy of annexin A2 via RAB11, RAB8A and RAB27A in IFN-γ-stimulated lung epithelial cells10.1038/s41598-017-06076-42045-2322https://doaj.org/article/bc911b52e59b49cab717a6b1e9b33d462017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06076-4https://doaj.org/toc/2045-2322Abstract Annexin A2 (ANXA2), a phospholipid-binding protein, has multiple biological functions depending on its cellular localization. We previously demonstrated that IFN-γ-triggered ANXA2 secretion is associated with exosomal release. Here, we show that IFN-γ-induced autophagy is essential for the extracellular secretion of ANXA2 in lung epithelial cells. We observed colocalization of ANXA2-containing autophagosomes with multivesicular bodies (MVBs) after IFN-γ stimulation, followed by exosomal release. IFN-γ-induced exophagic release of ANXA2 could not be observed in ATG5-silenced or mutant RAB11-expressing cells. Furthermore, knockdown of RAB8A and RAB27A, but not RAB27B, reduced IFN-γ-triggered ANXA2 secretion. Surface translocation of ANXA2 enhanced efferocytosis by epithelial cells, and inhibition of different exophagic steps, including autophagosome formation, fusion of autophagosomes with MVBs, and fusion of amphisomes with plasma membrane, reduced ANXA2-mediated efferocytosis. Our data reveal a novel route of IFN-γ-induced exophagy of ANXA2.Ying-Da ChenYi-Ting FangYi-Lin ChengChiou-Feng LinLi-Jin HsuShu-Ying WangRobert AndersonChih-Peng ChangYee-Shin LinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ying-Da Chen Yi-Ting Fang Yi-Lin Cheng Chiou-Feng Lin Li-Jin Hsu Shu-Ying Wang Robert Anderson Chih-Peng Chang Yee-Shin Lin Exophagy of annexin A2 via RAB11, RAB8A and RAB27A in IFN-γ-stimulated lung epithelial cells
description	Abstract Annexin A2 (ANXA2), a phospholipid-binding protein, has multiple biological functions depending on its cellular localization. We previously demonstrated that IFN-γ-triggered ANXA2 secretion is associated with exosomal release. Here, we show that IFN-γ-induced autophagy is essential for the extracellular secretion of ANXA2 in lung epithelial cells. We observed colocalization of ANXA2-containing autophagosomes with multivesicular bodies (MVBs) after IFN-γ stimulation, followed by exosomal release. IFN-γ-induced exophagic release of ANXA2 could not be observed in ATG5-silenced or mutant RAB11-expressing cells. Furthermore, knockdown of RAB8A and RAB27A, but not RAB27B, reduced IFN-γ-triggered ANXA2 secretion. Surface translocation of ANXA2 enhanced efferocytosis by epithelial cells, and inhibition of different exophagic steps, including autophagosome formation, fusion of autophagosomes with MVBs, and fusion of amphisomes with plasma membrane, reduced ANXA2-mediated efferocytosis. Our data reveal a novel route of IFN-γ-induced exophagy of ANXA2.
format	article
author	Ying-Da Chen Yi-Ting Fang Yi-Lin Cheng Chiou-Feng Lin Li-Jin Hsu Shu-Ying Wang Robert Anderson Chih-Peng Chang Yee-Shin Lin
author_facet	Ying-Da Chen Yi-Ting Fang Yi-Lin Cheng Chiou-Feng Lin Li-Jin Hsu Shu-Ying Wang Robert Anderson Chih-Peng Chang Yee-Shin Lin
author_sort	Ying-Da Chen
title	Exophagy of annexin A2 via RAB11, RAB8A and RAB27A in IFN-γ-stimulated lung epithelial cells
title_short	Exophagy of annexin A2 via RAB11, RAB8A and RAB27A in IFN-γ-stimulated lung epithelial cells
title_full	Exophagy of annexin A2 via RAB11, RAB8A and RAB27A in IFN-γ-stimulated lung epithelial cells
title_fullStr	Exophagy of annexin A2 via RAB11, RAB8A and RAB27A in IFN-γ-stimulated lung epithelial cells
title_full_unstemmed	Exophagy of annexin A2 via RAB11, RAB8A and RAB27A in IFN-γ-stimulated lung epithelial cells
title_sort	exophagy of annexin a2 via rab11, rab8a and rab27a in ifn-γ-stimulated lung epithelial cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/bc911b52e59b49cab717a6b1e9b33d46
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Exophagy of annexin A2 via RAB11, RAB8A and RAB27A in IFN-γ-stimulated lung epithelial cells

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