T cell homeostasis is essential for the functioning of the vertebrate immune system, but the intracellular signals required for T cell homeostasis are largely unknown. We here report that the WD-repeat protein family member coronin-1, encoded by the gene Coro1a, is essential in the mouse for T cell survival through its promotion of Ca2+ mobilization from intracellular stores. Upon T cell receptor triggering, coronin-1 was essential for the generation of inositol-1,4,5-trisphosphate from phosphatidylinositol-4,5-bisphosphate. The absence of coronin-1, although it did not affect T cell development, resulted in a profound defect in Ca2+ mobilization, interleukin-2 production, T cell proliferation and T cell survival. We conclude that coronin-1, through activation of Ca2+ release from intracellular stores, is an essential regulator of peripheral lymphocyte survival.
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We thank L. Kuhn for assistance with two-dimensional SDS-PAGE and J. Kirberg, K. Huygen, H. Korf, V. Jaeggin, E. Teixeiro, M. Daniels, E. Palmer and P. Demougin for help and discussions. Supported by the German Research Council (SFB 497-B5 to H.-R.R.) and the Kanton Basel-Stadt as well as the Swiss National Science Foundation (to J.P.).
Supplementary Methods, Supplementary Figures 1–8, Supplementary Table 1 (PDF 2295 kb)
Normal cell spreading of wild-type T cells seeded on polylysine coated slides (control); time-lapse images were acquired every 10 seconds for 30 minutes. (MOV 929 kb)
Normal cell spreading of Coronin-1-deficient T cells seeded on polylysine coated slides (control); time-lapse images were acquired every 10 seconds for 30 minutes. (MOV 909 kb)
Normal TCR-mediated cell spreading of wild-type T cells seeded on anti-CD3 + anti-CD28 coated slides; time-lapse images were acquired every 10 seconds for 30 minutes. (MOV 2048 kb)
Normal TCR-mediated cell spreading of Coronin-1-deficient T cells seeded on anti-CD3 + anti-CD28 coated slides; time-lapse images were acquired every 10 seconds for 30 minutes. (MOV 1903 kb)
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Mueller, P., Massner, J., Jayachandran, R. et al. Regulation of T cell survival through coronin-1–mediated generation of inositol-1,4,5-trisphosphate and calcium mobilization after T cell receptor triggering. Nat Immunol 9, 424–431 (2008). https://doi.org/10.1038/ni1570
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