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Tespa1 regulates T cell receptor-induced calcium signals by recruiting inositol 1,4,5-trisphosphate receptors

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Listed:
  • Jingjing Liang

    (Institute of Immunology, Zhejiang University School of Medicine
    Program in Molecular and Cellular Biology, Zhejiang University School of Medicine)

  • Jun Lyu

    (Institute of Immunology, Zhejiang University School of Medicine
    Program in Molecular and Cellular Biology, Zhejiang University School of Medicine)

  • Meng Zhao

    (Ministry of Education Key Laboratory of Protein Sciences, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Institute for Immunology, School of Life Sciences, Tsinghua University)

  • Dan Li

    (Institute of Immunology, Zhejiang University School of Medicine
    Program in Molecular and Cellular Biology, Zhejiang University School of Medicine)

  • Mingzhu Zheng

    (Institute of Immunology, Zhejiang University School of Medicine
    Program in Molecular and Cellular Biology, Zhejiang University School of Medicine)

  • Yan Fang

    (Ministry of Education Key Laboratory of Protein Sciences, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Institute for Immunology, School of Life Sciences, Tsinghua University)

  • Fangzhu Zhao

    (Institute of Immunology, Zhejiang University School of Medicine)

  • Jun Lou

    (Institute of Immunology, Zhejiang University School of Medicine
    Program in Molecular and Cellular Biology, Zhejiang University School of Medicine)

  • Chuansheng Guo

    (Institute of Immunology, Zhejiang University School of Medicine
    Program in Molecular and Cellular Biology, Zhejiang University School of Medicine)

  • Lie Wang

    (Institute of Immunology, Zhejiang University School of Medicine)

  • Di Wang

    (Institute of Immunology, Zhejiang University School of Medicine
    Program in Molecular and Cellular Biology, Zhejiang University School of Medicine)

  • Wanli Liu

    (Ministry of Education Key Laboratory of Protein Sciences, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Institute for Immunology, School of Life Sciences, Tsinghua University)

  • Linrong Lu

    (Institute of Immunology, Zhejiang University School of Medicine
    Program in Molecular and Cellular Biology, Zhejiang University School of Medicine
    ZJU-UoE Institute, Zhejiang University School of Medicine
    Innovation Center for Cell Signaling Network, Zhejiang University School of Medicine)

Abstract

Thymocyte-expressed, positive selection-associated 1 (Tespa1) is important in T cell receptor (TCR)-driven thymocyte development. Downstream of the TCR, Tespa1 is a crucial component of the linker for activation of T cells (LAT) signalosome, facilitating calcium signalling and subsequent MAPK activation. However, it is unknown how Tespa1 elicits calcium signalling. Here, we show that inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) is crucial for Tespa1-optimized, TCR-induced Ca2+ flux and thymocyte development. Upon TCR stimulation, Tespa1 directly interacts with IP3R1 and recruits it to the TCR complex, where IP3R1 is phosphorylated at Y353 by Fyn. This Tespa1-IP3R1 interaction is mediated by the F187 and F188 residues of Tespa1 and the amino-terminus of IP3R1. Tespa1-F187A/F188A mutant mice phenocopy Tespa1-deficient mice with impaired late thymocyte development due to reduced IP3R1 translocation to the TCR-proximal region. Our work elucidates the function of Tespa1 in T cell development and the regulation of TCR-induced Ca2+ signalling through IP3R1.

Suggested Citation

  • Jingjing Liang & Jun Lyu & Meng Zhao & Dan Li & Mingzhu Zheng & Yan Fang & Fangzhu Zhao & Jun Lou & Chuansheng Guo & Lie Wang & Di Wang & Wanli Liu & Linrong Lu, 2017. "Tespa1 regulates T cell receptor-induced calcium signals by recruiting inositol 1,4,5-trisphosphate receptors," Nature Communications, Nature, vol. 8(1), pages 1-13, August.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15732
    DOI: 10.1038/ncomms15732
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