Abstract
New functions are implicated for calreticulin, based on its release from cytotoxic NK and T cells. Calreticulin is the only one of six “KDEL” (Lys-Asp-Glu-Leu carboxy terminal) endoplasmic reticulum chaperone proteins present in cytotoxic granules of these lymphocytes. Calreticulin is released when the lymphocytes release their granules to kill other cells, which suggests that it is likely to have an important role. In this chapter, we briefly review the contents of cytotoxic granules and how calreticulin might interact with these proteins. Then we discuss calreticulin inactivation of lysis mediated by perforin, a pore-forming protein which is essential for granule-mediated toxicity. Calreticulin is degraded by granzymes (proteases found within the cytotoxic granules), particularly by one granzyme, Chymase 1. Chymase 1 was previously identified as required for granule-mediated lysis, which could indicate that the calreticulin function(s) may be temporally regulated. We also introduce our “inactivation of the inactivator” hypothesis (granzyme-degradation of the inactivator calreticulin) as a focus for evaluation of the present information and as a focus to identify critical information to collect in the future. Finally, we provide the reader with additional functions of calreticulin that could be important for systemic immunity.
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Hudig, D., Karimi, R. (2003). Calreticulin in Cytotoxic Lymphocyte-Mediated Cytotoxicity. In: Eggleton, P., Michalak, M. (eds) Calreticulin. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9258-1_14
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DOI: https://doi.org/10.1007/978-1-4419-9258-1_14
Publisher Name: Springer, Boston, MA
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