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

Jingjing Liang, Jun Lyu, Meng Zhao, Dan Li, Mingzhu Zheng, Yan Fang, Fangzhu Zhao, Jun Lou, Chuansheng Guo, Lie Wang, Di Wang, Wanli Liu () and Linrong Lu ()
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Jingjing Liang: Institute of Immunology, Zhejiang University School of Medicine
Jun Lyu: Institute of Immunology, 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
Mingzhu Zheng: Institute of Immunology, 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
Chuansheng Guo: Institute of Immunology, 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
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

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms15732

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