Perforin-mediated target-cell death and immune homeostasis.
The granule exocytosis pathway of cytotoxic lymphocytes is crucial for immune surveillance and homeostasis. The trafficking of granule components, including the membrane-disruptive protein perforin, to the immunological synapse leads to the delivery of granule proteases (granzymes) into the target cell and its destruction through apoptosis. Several independent molecular abnormalities associated with defects of either granule trafficking or perforin function can cause cytotoxic lymphocyte dysfunction. In humans, inherited perforin mutations result in severe immune dysregulation that manifests as familial haemophagocytic lymphohistiocytosis. This Review describes recent progress in defining the structure, function, biochemistry and cell biology of perforin.
Voskoboinik
Ilia
I
Cancer Immunology Program, Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Victoria 3002, Australia. ilia.voskoboinik@petermac.org
Smyth
Mark J
MJ
Trapani
Joseph A
JA
D000818:Animals; D016923:Cell Death / Q000235:genetics; D005089:Exocytosis / Q000235:genetics; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009154:Mutation; D054353:Perforin; D011110:Polymorphism, Genetic; D052899:Pore Forming Cytotoxic Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin