Perforin: structure, function, and role in human immunopathology
Ilia Voskoboinik, Michelle A Dunstone, Katherine Baran, James C Whisstock, Joseph A Trapani
Immunological Reviews | WILEY | Published : 2010
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 ..View full abstract
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he authors gratefully acknowledge the contributions made by many former laboratory members, graduate students and collaborators to the findings summarized here. We are also extremely grateful for the generous financial support that underpins our work: all of the authors are supported by Program and/or Project Grants from the National Health and Medical Research Council (NHMRC) of Australia. J. A. T. is a Senior Principal Research Fellow, and I. V. and M. A. D. hold career development awards from NHMRC. J. A. T receives Program Grant support from the Juvenile Diabetes Research Foundation (JDRF) USA. J. C. W is a Federation Fellow of the Australian Research Council.