Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Regulation of T cell survival through coronin-1–mediated generation of inositol-1,4,5-trisphosphate and calcium mobilization after T cell receptor triggering

Nature Immunology volume 9, pages 424–431 (2008)Cite this article

Abstract

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: T cell cytoskeleton and F-actin dynamics in the presence and absence of coronin-1.
Figure 2: T cell proliferation and cycling in the presence and absence of coronin-1.
Figure 3: T cell signaling, InsP3 generation and localization of signaling molecules.
Figure 4: PtdIns(4,5)P2 localization and Ca2+ mobilization in wild-type and coronin-1–deficient T cells.
Figure 5: Thymocyte coronin-1 and Ca2+ flux.
Figure 6: Signaling pathways in wild-type and coronin-1–deficient cells upon TCR and PLC activation.
Figure 7: Interaction of Coronin-1 and PLC-γ1.

Similar content being viewed by others

References

  1. Starr, T.K., Jameson, S.C. & Hogquist, K.A. Positive and negative selection of T cells. Annu. Rev. Immunol. 21, 139–176 (2003).

    Article  CAS  PubMed  Google Scholar 

  2. Sprent, J. & Tough, D.F. T cell death and memory. Science 293, 245–248 (2001).

    Article  CAS  PubMed  Google Scholar 

  3. Goldrath, A.W. & Bevan, M.J. Selecting and maintaining a diverse T-cell repertoire. Nature 402, 255–262 (1999).

    Article  CAS  PubMed  Google Scholar 

  4. Jameson, S.C. Maintaining the norm: T-cell homeostasis. Nat. Rev. Immunol. 2, 547–556 (2002).

    Article  CAS  PubMed  Google Scholar 

  5. Takeda, S., Rodewald, H.R., Arakawa, H., Bluethmann, H. & Shimizu, T. MHC class II molecules are not required for survival of newly generated CD4+ T cells, but affect their long-term life span. Immunity 5, 217–228 (1996).

    Article  CAS  PubMed  Google Scholar 

  6. Kirberg, J., Berns, A. & von Boehmer, H. Peripheral T cell survival requires continual ligation of the T cell receptor to major histocompatibility complex-encoded molecules. J. Exp. Med. 186, 1269–1275 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Polic, B., Kunkel, D., Scheffold, A. & Rajewsky, K. How alpha beta T cells deal with induced TCR alpha ablation. Proc. Natl. Acad. Sci. USA 98, 8744–8749 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Labrecque, N. et al. How much TCR does a T cell need? Immunity 15, 71–82 (2001).

    Article  CAS  PubMed  Google Scholar 

  9. Gatfield, J., Albrecht, I., Zanolari, B., Steinmetz, M.O. & Pieters, J. Association of the leukocyte plasma membrane with the actin cytoskeleton through coiled coil-mediated trimeric coronin 1 molecules. Mol. Biol. Cell 16, 2786–2798 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Foger, N., Rangell, L., Danilenko, D.M. & Chan, A.C. Requirement for coronin 1 in T lymphocyte trafficking and cellular homeostasis. Science 313, 839–842 (2006).

    Article  PubMed  Google Scholar 

  11. Jayachandran, R. et al. Survival of mycobacteria in macrophages is mediated by coronin 1-dependent activation of calcineurin. Cell 130, 37–50 (2007).

    Article  CAS  PubMed  Google Scholar 

  12. Jayachandran, J. et al. RNA interference in J774 macrophages reveals a role for coronin 1 in mycobacterial trafficking but not in actin-dependent processes. Mol. Biol. Cell (in the press).

  13. Gallo, E.M., Cante-Barrett, K. & Crabtree, G.R. Lymphocyte calcium signaling from membrane to nucleus. Nat. Immunol. 7, 25–32 (2006).

    Article  CAS  PubMed  Google Scholar 

  14. Lewis, R.S. Calcium signaling mechanisms in T lymphocytes. Annu. Rev. Immunol. 19, 497–521 (2001).

    Article  CAS  PubMed  Google Scholar 

  15. Zhang, W., Wu, Y., Du, L., Tang, D.D. & Gunst, S.J. Activation of the Arp2/3 complex by N-WASp is required for actin polymerization and contraction in smooth muscle. Am. J. Physiol. Cell Physiol. 288, C1145–C1160 (2005).

    Article  CAS  PubMed  Google Scholar 

  16. Bunnell, S.C., Kapoor, V., Trible, R.P., Zhang, W. & Samelson, L.E. Dynamic actin polymerization drives T cell receptor-induced spreading: a role for the signal transduction adaptor LAT. Immunity 14, 315–329 (2001).

    Article  CAS  PubMed  Google Scholar 

  17. Nolz, J.C. et al. The WAVE2 complex regulates actin cytoskeletal reorganization and CRAC-mediated calcium entry during T cell activation. Curr. Biol. 16, 24–34 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Murali-Krishna, K. et al. Persistence of memory CD8 T cells in MHC class I-deficient mice. Science 286, 1377–1381 (1999).

    Article  CAS  PubMed  Google Scholar 

  19. Swain, S.L. CD4 T-cell memory can persist in the absence of class II. Phil. Trans. R. Soc. Lond. B 355, 407–411 (2000).

    Article  CAS  Google Scholar 

  20. Huang, Y. & Wange, R.L. T cell receptor signaling: beyond complex complexes. J. Biol. Chem. 279, 28827–28830 (2004).

    Article  CAS  PubMed  Google Scholar 

  21. Zhang, W., Sloan-Lancaster, J., Kitchen, J., Trible, R.P. & Samelson, L.E. LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. Cell 92, 83–92 (1998).

    Article  CAS  PubMed  Google Scholar 

  22. Altman, A. & Villalba, M. Protein kinase C-theta (PKCθ): it's all about location, location, location. Immunol. Rev. 192, 53–63 (2003).

    Article  CAS  PubMed  Google Scholar 

  23. Thastrup, O., Cullen, P.J., Drobak, B.K., Hanley, M.R. & Dawson, A.P. Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2+-ATPase. Proc. Natl. Acad. Sci. USA 87, 2466–2470 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Nal, B. et al. Coronin-1 expression in T lymphocytes: insights into protein function during T cell development and activation. Int. Immunol. 16, 231–240 (2004).

    Article  CAS  PubMed  Google Scholar 

  25. Nakayama, T. et al. Inhibition of T cell receptor expression and function in immature CD4+CD8+ cells by CD4. Science 249, 1558–1561 (1990).

    Article  CAS  PubMed  Google Scholar 

  26. Okumura, M., Kung, C., Wong, S., Rodgers, M. & Thomas, M.L. Definition of family of coronin-related proteins conserved between humans and mice: close genetic linkage between coronin-2 and CD45-associated protein. DNA Cell Biol. 17, 779–787 (1998).

    Article  CAS  PubMed  Google Scholar 

  27. Marrack, P. & Kappler, J. Control of T cell viability. Annu. Rev. Immunol. 22, 765–787 (2004).

    Article  CAS  PubMed  Google Scholar 

  28. Farber, D.L. Differential TCR signaling and the generation of memory T cells. J. Immunol. 160, 535–539 (1998).

    CAS  PubMed  Google Scholar 

  29. Farber, D.L., Acuto, O. & Bottomly, K. Differential T cell receptor-mediated signaling in naive and memory CD4 T cells. Eur. J. Immunol. 27, 2094–2101 (1997).

    Article  CAS  PubMed  Google Scholar 

  30. Roederer, M. et al. Heterogeneous calcium flux in peripheral T cell subsets revealed by five-color flow cytometry using log-ratio circuitry. Cytometry 21, 187–196 (1995).

    Article  CAS  PubMed  Google Scholar 

  31. Denys, A., Aires, V., Hichami, A. & Khan, N.A. Thapsigargin-stimulated MAP kinase phosphorylation via CRAC channels and PLD activation: inhibitory action of docosahexaenoic acid. FEBS Lett. 564, 177–182 (2004).

    Article  CAS  PubMed  Google Scholar 

  32. Ebinu, J.O. et al. RasGRP links T-cell receptor signaling to Ras. Blood 95, 3199–3203 (2000).

    CAS  PubMed  Google Scholar 

  33. Bae, Y.S. et al. Identification of a compound that directly stimulates phospholipase C activity. Mol. Pharmacol. 63, 1043–1050 (2003).

    Article  CAS  PubMed  Google Scholar 

  34. Tulp, A., Verwoerd, D., Dobberstein, B., Ploegh, H.L. & Pieters, J. Isolation and characterization of the intracellular MHC class II compartment. Nature 369, 120–126 (1994).

    Article  CAS  PubMed  Google Scholar 

  35. Gatfield, J. & Pieters, J. Essential role for cholesterol in entry of mycobacteria into macrophages. Science 288, 1647–1650 (2000).

    Article  CAS  PubMed  Google Scholar 

  36. Lee, W.T., Cole-Calkins, J. & Street, N.E. Memory T cell development in the absence of specific antigen priming. J. Immunol. 157, 5300–5307 (1996).

    CAS  PubMed  Google Scholar 

  37. Saparov, A. et al. Memory/effector T cells in TCR transgenic mice develop via recognition of enteric antigens by a second, endogenous TCR. Int. Immunol. 11, 1253–1264 (1999).

    Article  CAS  PubMed  Google Scholar 

  38. Ferrari, G., Langen, H., Naito, M. & Pieters, J. A coat protein on phagosomes involved in the intracellular survival of mycobacteria. Cell 97, 435–447 (1999).

    Article  CAS  PubMed  Google Scholar 

  39. Pieters, J. Evasion of host cell defense mechanisms by pathogenic bacteria. Curr. Opin. Immunol. 13, 37–44 (2001).

    Article  CAS  PubMed  Google Scholar 

  40. Suzuki, K. et al. Molecular cloning of a novel actin-binding protein, p57, with a WD repeat and a leucine zipper motif. FEBS Lett. 364, 283–288 (1995).

    Article  CAS  PubMed  Google Scholar 

  41. Yang, L.J., Rhee, S.G. & Williamson, J.R. Epidermal growth factor-induced activation and translocation of phospholipase C-gamma 1 to the cytoskeleton in rat hepatocytes. J. Biol. Chem. 269, 7156–7162 (1994).

    CAS  PubMed  Google Scholar 

  42. Singer, W.D., Brown, H.A. & Sternweis, P.C. Regulation of eukaryotic phosphatidylinositol-specific phospholipase C and phospholipase D. Annu. Rev. Biochem. 66, 475–509 (1997).

    Article  CAS  PubMed  Google Scholar 

  43. Pieters, J., Horstmann, H., Bakke, O., Griffiths, G. & Lipp, J. Intracellular transport and localization of major histocompatibility complex class II molecules and associated invariant chain. J. Cell Biol. 115, 1213–1223 (1991).

    Article  CAS  PubMed  Google Scholar 

  44. Barda-Saad, M. et al. Dynamic molecular interactions linking the T cell antigen receptor to the actin cytoskeleton. Nat. Immunol. 6, 80–89 (2005).

    Article  CAS  PubMed  Google Scholar 

  45. Teixeiro, E. et al. T cell division and death are segregated by mutation of TCRβ chain constant domains. Immunity 21, 515–526 (2004).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

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.).

Author information

Author notes

  1. Philipp Mueller, Jan Massner and Rajesh Jayachandran: These authors contributed equally to this work.

Authors and Affiliations

  1. Biozentrum, University of Basel, Klingelbergstrasse 50-70, Basel, CH 4056, Switzerland

    Philipp Mueller, Jan Massner, Rajesh Jayachandran, Benoit Combaluzier, Imke Albrecht, John Gatfield & Jean Pieters

  2. Institute for Immunology, University of Ulm, Germany

    Carmen Blum & Hans-Reimer Rodewald

  3. Department of Clinical Biological Sciences, University of Basel, Mattenstrasse 28, Basel, CH 4058, Switzerland

    Rod Ceredig & Antonius G Rolink

Authors
  1. Philipp Mueller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jan Massner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rajesh Jayachandran
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Benoit Combaluzier
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Imke Albrecht
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. John Gatfield
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Carmen Blum
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rod Ceredig
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hans-Reimer Rodewald
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jean Pieters
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

P.M. performed the experiments unless stated otherwise; J.M. generated the coronin-1–deficient mice and performed their phenotypic analysis (shown in Supplementary Figs. 1, 2, 3 and Fig. 2a) with contributions from I.A., B.C., C.B., R.C., H.-R.R. and A.G.R.; J.G. generated the siRNA used in Jurkat T cells and R.J. performed the video microscopy, m-3M3FBS experiments and PtdIns(4,5)P2 analysis as well as the experiments presented in Figures 1b and 3g; R.J. and B.C. together with P.M. performed the experiments shown in Supplementary Figure 6; J.P. coordinated as well as supervised the project and prepared the manuscript.

Corresponding author

Correspondence to Jean Pieters.

Supplementary information

Supplementary Text and Figures

Supplementary Methods, Supplementary Figures 1–8, Supplementary Table 1 (PDF 2295 kb)

Supplementary Video 1

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)

Supplementary Video 2

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)

Supplementary Video 3

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)

Supplementary Video 4

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)

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ni1570

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing