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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doaj-bc911b52e59b49cab717a6b1e9b33d462020-12-08T00:37:31ZengNature Publishing GroupScientific Reports2045-23222017-07-017111310.1038/s41598-017-06076-4Exophagy of annexin A2 via RAB11, RAB8A and RAB27A in IFN-γ-stimulated lung epithelial cellsYing-Da Chen0Yi-Ting Fang1Yi-Lin Cheng2Chiou-Feng Lin3Li-Jin Hsu4Shu-Ying Wang5Robert Anderson6Chih-Peng Chang7Yee-Shin Lin8Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung UniversityDepartment of Microbiology and Immunology, College of Medicine, National Cheng Kung UniversityInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung UniversityCenter of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung UniversityInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung UniversityInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung UniversityCenter of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung UniversityInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung UniversityInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung UniversityAbstract 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.https://doi.org/10.1038/s41598-017-06076-4 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-07-01 |
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. |
url |
https://doi.org/10.1038/s41598-017-06076-4 |
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