The ABCs of granule-mediated cytotoxicity: new weapons in the arsenal.
Granule exocytosis is the main pathway for the immune elimination of virus-infected cells and tumour cells by cytotoxic T lymphocytes and natural killer cells. After target-cell recognition, release of the cytotoxic granule contents into the immunological synapse formed between the killer cell and its target induces apoptosis. The granules contain two membrane-perturbing proteins, perforin and granulysin, and a family of serine proteases known as granzymes, complexed with the proteoglycan serglycin. In this review, I discuss recent insights into the mechanisms of granule-mediated cytotoxicity, focusing on how granzymes A, B and C and granulysin activate cell death through caspase-independent pathways.
Lieberman
Judy
J
Center for Blood Research and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA. lieberman@cbr.med.harvard.edu
D000818:Animals; D017209:Apoptosis; D003602:Cytotoxicity, Immunologic; D005089:Exocytosis; D053804:Granzymes; D051379:Mice; D018448:Models, Immunological; D022142:Secretory Vesicles / Q000737:chemistry / Q000201:enzymology*; D012697:Serine Endopeptidases / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D053804:Granzymes; C509214:Gzmb protein, mouse; C509216:Gzmc protein, mouse; D012697:Serine Endopeptidases