title: Tespa1 negatively regulates FcεRI-mediated signaling and the mast cell-mediated allergic response.
abstract: Antigen-mediated cross-linking of IgE on mast cells triggers a signaling cascade that results in their degranulation and proinflammatory cytokine production, which are key effectors in allergic reactions. We show that the activation of mast cells is negatively regulated by the newly identified adaptor protein Tespa1. Loss of Tespa1 in mouse mast cells led to hyper-responsiveness to stimulation via FcεRI. Mice lacking Tespa1 also displayed increased sensitivity to IgE-mediated allergic responses. The dysregulated signaling in KO mast cells was associated with increased activation of Grb2-PLC-γ1-SLP-76 signaling within the LAT1 (linker for activation of T cells family, member 1) signalosome versus the LAT2 signalosome. Collectively, these findings show that Tespa1 orchestrates mast cell activation by tuning the balance of LAT1 and LAT2 signalosome assembly.
authors.affiliation: Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China diwang@zju.edu.cn lu_linrong@zju.edu.cn.
authors.forename: Di
authors.initials: D
authors.lastname: Wang
authors.affiliation: Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Yuanjun
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Chuansheng
authors.initials: C
authors.lastname: Guo
authors.affiliation: Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ji
authors.affiliation: Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.affiliation: Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liang
authors.affiliation: Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lou
authors.affiliation: Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Dong
authors.affiliation: Medical College of Lishui University, Lishui, Zhejiang 323000, China.
authors.forename: Songquan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Jianli
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Yuehai
authors.initials: Y
authors.lastname: Ke
authors.affiliation: Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
authors.affiliation: Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Yi Ting
authors.initials: YT
authors.lastname: Zhou
authors.affiliation: Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China Institute of Immunology, Program in Molecular and Cellular Biology, Department of Pathology and Pathophysiology, and Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou 310058, China diwang@zju.edu.cn lu_linrong@zju.edu.cn.
authors.forename: Linrong
authors.initials: L
authors.lastname: Lu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000378:metabolism*; D027182:Amino Acid Transport System y+ / Q000378:metabolism; D027241:Amino Acid Transport System y+L; D000707:Anaphylaxis / Q000276:immunology; D000818:Animals; D015550:Cell Degranulation; D002465:Cell Movement; D018925:Chemokines / Q000096:biosynthesis; D027301:Fusion Regulatory Protein 1, Light Chains / Q000378:metabolism; D006967:Hypersensitivity / Q000276:immunology* / Q000473:pathology; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017455:Receptors, IgE / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D027182:Amino Acid Transport System y+; D027241:Amino Acid Transport System y+L; D018925:Chemokines; C579617:FcepsilonRIalpha protein, mouse; D027301:Fusion Regulatory Protein 1, Light Chains; D017455:Receptors, IgE; C518286:SLC7A8 protein, mouse; C518287:Slc7a7 protein, mouse; C574974:Tespa1 protein, mouse