The secretory granule-mediated cell death pathway is the key mechanism for elimination of virus-infected and transformed target cells by cytotoxic lymphocytes. The formation of the immunological synapse between an effector and a target cell leads to exocytic trafficking of the secretory granules and the release of their contents, which include pro-apoptotic serine proteases, granzymes, and pore-forming perforin into the synapse. There, perforin polymerizes and forms a transmembrane pore that allows the delivery of granzymes into the cytosol, where they initiate various apoptotic death pathways. Unlike relatively redundant individual granzymes, functional perforin is absolutely essential for cytotoxic lymphocyte function and immune regulation in the host. Nevertheless, perforin is still the least studied and understood cytotoxic molecule in the immune system. In this review, we discuss the current state of affairs in the perforin field: the protein's structure and function as well as its role in immune-mediated diseases.
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| http://dx.doi.org/10.1111/j.0105-2896.2010.00896.x | DOI Listing |
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