title: S100A10 Regulates ULK1 Localization to ER-Mitochondria Contact Sites in IFN-γ-Triggered Autophagy.
abstract: During the process of autophagy, the autophagy-related proteins are translocated to autophagosome formation sites. Here, we demonstrate that S100A10 is required for ULK1 localization to autophagosome formation sites. Silencing of S100A10 reduces IFN-γ-induced autophagosome formation. We also determined the role of annexin A2 (ANXA2), a binding partner of S100A10, which has been reported to promote phagophore assembly. Silencing of ANXA2 reduced S100A10 expression. However, overexpression of S100A10 in ANXA2-silenced cells was still able to enhance autophagosome formation, suggesting that ANXA2 regulates IFN-γ-induced autophagy through S100A10. We also observed that S100A10 interacted with ULK1 after IFN-γ stimulation, and S100A10 knockdown prevented ULK1 localization to autophagosome formation sites. Finally, the release of high mobility group protein B1, one of the functions mediated by IFN-γ-induced autophagy, was inhibited in S100A10 knockdown cells. These results elucidate the importance of S100A10 in autophagosome formation and reveal the relationship between S100A10 and ULK1 in IFN-γ-induced autophagy.
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Ying-Da
authors.initials: YD
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Fang
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan; Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Chih-Peng
authors.initials: CP
authors.lastname: Chang
authors.affiliation: Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan; Department of Microbiology and Immunology, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
authors.forename: Chiou-Feng
authors.initials: CF
authors.lastname: Lin
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan; Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan; Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Li-Jin
authors.initials: LJ
authors.lastname: Hsu
authors.affiliation: Institute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Shang-Rung
authors.initials: SR
authors.lastname: Wu
authors.affiliation: Institute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Yen-Chi
authors.initials: YC
authors.lastname: Chiu
authors.affiliation: Departments of Microbiology & Immunology and Pediatrics, and Canadian Center for Vaccinology, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Anderson
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan; Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan. Electronic address: yslin1@mail.ncku.edu.tw.
authors.forename: Yee-Shin
authors.initials: YS
authors.lastname: Lin
mesh_terms: D017306:Annexin A2 / Q000378:metabolism*; D001343:Autophagy; D000071189:Autophagy-Related Protein-1 Homolog / Q000378:metabolism*; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D021381:Protein Transport; D009418:S100 Proteins / Q000378:metabolism*; D000099248:S100 Calcium Binding Protein A10
chemical_list: D017306:Annexin A2; D000071189:Autophagy-Related Protein-1 Homolog; D024243:HMGB1 Protein; D007371:Interferon-gamma; D047908:Intracellular Signaling Peptides and Proteins; D009418:S100 Proteins; D000099248:S100 Calcium Binding Protein A10; C472822:ANXA2 protein, human; C585491:HMGB1 protein, human; C484754:ULK1 protein, human
keywords: HMGB1; S100A10; ULK1 translocation; autophagosome formation; interferon-γ