This week, Nature Communications published the latest research from Prof. Linrong LU’s team, together with Prof. Wanli LIU in Tsinghua University. The article named “Tespa1 regulates T cell receptor-induced calcium signals by recruiting inositol 1,4,5-trisphosphate receptors” illustrated the regulatory mechanism of how adaptor protein Tesap1 facilitates the calcium signaling downstream of T cell receptor.
T cell is one of the crucial immune cells which is developed in thymus. The late development of thymic T cell depends on the signal of TCR. The TCR signal plays a vital role in T cell maturation. It not only enables the T cells to respond to MHC-restricted antigen after they mature, but also helps to establish immune tolerance towards self.
In 2012, Nature Immunology published a research paper from Prof. Linrong LU’s team “Tespa1 is involved in late thymocyte development through the regulation of TCR-mediated signaling”, in which, they discovered and named a new signaling molecule Tespa1 which is involved in regulating TCR signaling as well as thymocyte development.
The current research further illustrates the molecular mechanism of Tespa1: when TCR receives the signal, Tespa1 gets associated with phospholipase PLCg1 in the TCR signal complex; it, at the same time, by means of it PFF motif, recruits calcium channel IP3Rs, and leads to the relocation of IP3Rs to TCR proximal region. The relocation of IP3Rs not only facilitates the phosphorylation of IP3Rs by the kinase Fyn on the cell membrane, but also accelerates their binding to IP3 (the ligand of IP3Rs), which insures the efficient activation of calcium signal. This work illustrates the mechanism how Tespa1 regulate TCR signal, and reveals the importance of calcium channel re-distribution during the process of TCR signal transduction.
The first author of this work is Doctor candidate Jingjing Liang and Jun Lyu together with Prof. Wangli LIU’s team of Tsinghua University, with help from Prof. Di WANG and Prof. Lie WANG. The corresponding authors are Prof. Linrong Lu and Prof. Wangli LIU. This work is supported by grants from National Science Foundation of China.