Calreticulin: A Granule-Protein by Default or Design?
Calreticulin is a major calcium binding protein normally found in the lumen of the endoplasmic reticulum (ER). When T lymphocytes were activated we observed an increase in the levels of calreticulin mRNA and protein (Burns et al. 1992). Initially we thought this induction might relate to the changes in intracellular Ca2+ levels that have been associated with signal transduction, ultimately leading to specific gene transcription and cell activation. However, subsequent experiments revealed that calreticulin itself can also directly influence patterns of steroid hormone-dependent gene expression by binding to the receptor protein (Burns et al. 1994a). This left us with somewhat of a conundrum: in order to influence gene expression calreticulin would have to find its way from the ER to the nucleus, possibly via the cytoplasm. We were very surprised to discover that, when we immunolocalized calreticulin in activated cytotoxic T cells (CTLs) the major positive organelles were none other than our old friends the cytoplasmic granules. Concomitantly a report appeared on the NH2-terminal sequence analysis of a 60 kDa granule-associated protein that copurifies with perforin. The peptide was identical to calreticulin (Dupuis et al. 1993).
KeywordsZinc Permeability Hydrolysis Cysteine Polypeptide
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