Delivering the kiss of death: progress on understanding how perforin works.
Killer lymphocytes release perforin and granzymes from cytotoxic granules into the immunological synapse to destroy target cells as a critical mechanism in the defense against viruses and cancer. Perforin, a Ca(2+)-dependent pore-forming protein that multimerizes in membranes, delivers granzymes into the target cell cytosol. The original model for perforin (acting by forming a cell membrane channel through which granzymes pass) does not fit the experimental data. Recently, an alternative model has been proposed that involves active target cell collaboration with perforin to deliver granzymes and direct the target cell to an apoptotic, rather than necrotic, death.
Pipkin
Matthew E
ME
CBR Institute for Biomedical Research, Harvard Medical School, Boston MA 02115, USA.
Lieberman
Judy
J
D000818:Animals; D003602:Cytotoxicity, Immunologic; D053804:Granzymes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D018448:Models, Immunological; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D053804:Granzymes