title: Hedgehog signaling controls T cell killing at the immunological synapse.
abstract: The centrosome is essential for cytotoxic T lymphocyte (CTL) function, contacting the plasma membrane and directing cytotoxic granules for secretion at the immunological synapse. Centrosome docking at the plasma membrane also occurs during cilia formation. The primary cilium, formed in nonhematopoietic cells, is essential for vertebrate Hedgehog (Hh) signaling. Lymphocytes do not form primary cilia, but we found and describe here that Hh signaling played an important role in CTL killing. T cell receptor activation, which "prearms" CTLs with cytotoxic granules, also initiated Hh signaling. Hh pathway activation occurred intracellularly and triggered Rac1 synthesis. These events "prearmed" CTLs for action by promoting the actin remodeling required for centrosome polarization and granule release. Thus, Hh signaling plays a role in CTL function, and the immunological synapse may represent a modified cilium.
authors: Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.
authors: Maike
authors: M
authors: de la Roche
authors: Alex T
authors: AT
authors: Ritter
authors: Karen L
authors: KL
authors: Angus
authors: Colin
authors: C
authors: Dinsmore
authors: Charles H
authors: CH
authors: Earnshaw
authors: Jeremy F
authors: JF
authors: Reiter
authors: Gillian M
authors: GM
authors: Griffiths
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016764:Cell Polarity; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D053823:Hedgehog Proteins / Q000378:metabolism*; D054992:Immunological Synapses; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018448:Models, Immunological; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D000072079:Patched Receptors; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D000072086:Smoothened Receptor; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C498520:Gli1 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009479:Neuropeptides; D000072079:Patched Receptors; C484602:Rac1 protein, mouse; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D000071676:Zinc Finger Protein GLI1; C514061:ihh protein, mouse; D020830:rac1 GTP-Binding Protein