Cytotoxic T lymphocyte exocytosis: bring on the SNAREs!
Despite our general understanding of membrane traffic, the molecular machinery at the immunological synapse (IS) that regulates exocytosis of lytic granules from cytotoxic T lymphocytes (CTLs) remains elusive. The identification of disease-causing mutations in the small GTPase Rab27a, priming factor Munc13-4 and fusion protein syntaxin11 has defined an important role for these proteins in CTL exocytosis. In addition, the demonstration of a direct interaction in vitro between Rab27a and Munc13-4 suggests the possibility that the Rab27a-Munc13-4 cascade might regulate CTL exocytosis by engaging SNAREs such as syntaxin11. We propose that these SNAREs are likely to mediate the fusion of lytic granules with the plasma membrane of the IS.
Hong
Wanjin
W
Membrane Biology Laboratory, Institute of Molecular and Cell Biology, Proteos, 61 Biopolis Drive, Singapore 138673, Singapore. mcbhwj@imcb.a-star.edu.sg
D000595:Amino Acid Sequence; D003594:Cytoplasmic Granules / Q000502:physiology; D005089:Exocytosis / Q000502:physiology*; D006801:Humans; D051359:Lymphohistiocytosis, Hemophagocytic / Q000209:etiology / Q000503:physiopathology; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology; D050765:Qa-SNARE Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D050600:SNARE Proteins / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000502:physiology; D000075745:rab27 GTP-Binding Proteins
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; D050600:SNARE Proteins; C485548:UNC13B protein, human; C507969:UNC13D protein, human; D000075745:rab27 GTP-Binding Proteins; C066694:RAB27A protein, human; D020691:rab GTP-Binding Proteins