title: The role of N-glycan modification of TNFR1 in inflammatory microglia activation.
abstract: Accumulating evidences demonstrated that microglia activation and the autocrine loop of tumor necrosis factor-α (TNFα) greatly contribute to the pathogenesis of several CNS diseases. TNFα exerts its biological effects by interacting with two different receptors: TNF receptor 1 (TNFR1) and TNFR2. The classic proinflammatory activity of TNFα is mainly mediated by TNFR1. In the present study, we found that TNFR1 was modificated by N-glycosylation on Asn151 and Asn202 in microglia. The N-glycosylation of TNFR1 could facilitate its capability of binding to TNFα and further promote the formation of TNFα autocrine loop in microglia stimulated by TNFα, resulting in excessive microglia activation and CNS inflammation. All these processes were related to TNFR1-mediated NF-κB pathways. Elimination of N-glycosylation did not affect the subcellular transportation and cell surface localization of TNFR1, but suppressed ligand-binding affinity. These findings indicated that the N-glycosylation of TNFR1 played an important role during microglia activation in CNS inflammation. By this study, we aimed to provide some valuable experimental evidence for a better understanding of the significance of protein glycosylation in microglia inflammatory activation and CNS disease.
authors.affiliation: Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226000, Jiangsu, People's Republic of China.|The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226000, Jiangsu, People's Republic of China.
authors.forename: Lijian
authors.initials: L
authors.lastname: Han
authors.affiliation: The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226000, Jiangsu, People's Republic of China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226000, Jiangsu, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
authors.affiliation: The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226000, Jiangsu, People's Republic of China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Sun
authors.affiliation: The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226000, Jiangsu, People's Republic of China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226000, Jiangsu, People's Republic of China.
authors.forename: Guizhou
authors.initials: G
authors.lastname: Zhu
authors.affiliation: The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226000, Jiangsu, People's Republic of China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226000, Jiangsu, People's Republic of China.|The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226000, Jiangsu, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226000, Jiangsu, People's Republic of China.|The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226000, Jiangsu, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226000, Jiangsu, People's Republic of China.
authors.forename: Wangrui
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226000, Jiangsu, People's Republic of China. kekaifu1@sina.com.
authors.forename: Kaifu
authors.initials: K
authors.lastname: Ke
authors.affiliation: The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226000, Jiangsu, People's Republic of China. shag@ntu.edu.cn.|Department of Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226000, Jiangsu, People's Republic of China. shag@ntu.edu.cn.
authors.forename: Aiguo
authors.initials: A
authors.lastname: Shen
mesh_terms: D000818:Animals; D006031:Glycosylation; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha
keywords: Microglia activation; N-glycosylation; NF-κB; TNFR1; TNFα