title: Cytohesin-associated scaffolding protein (CASP) is involved in migration and IFN-γ secretion in natural killer cells.
abstract: Natural Killer (NK) cells are highly mobile, specialized sub-populations of lymphocytic cells that survey their host to identify and eliminate infected or tumor cells. They are one of the key players in innate immunity and do not need prior activation through antigen recognition to deliver cytotoxic packages and release messenger chemicals to recruit immune cells. Cytohesin associated scaffolding protein (CASP) is a highly expressed lymphocyte adaptor protein that forms complexes with vesicles and sorting proteins including SNX27 and Cytohesin-1. In this study we show that by using stably integrated shRNA, CASP has a direct role in the secretion of IFN-γ, and NK cell motility and ability to kill tumor cells. CASP polarizes to the leading edge of migrating NK cells, and to the immunological synapse when engaged with tumor cells. However, CASP is not associated with cytotoxic granule mediated killing. CASP is a multi-faceted protein, which has a very diverse role in NK cell specific immune functions.
authors: Department of Biology, Dalhousie University, Canada.
authors: Nicholas
authors: N
authors: Tompkins
authors: Department of Biology, Dalhousie University, Canada.
authors: Brian
authors: B
authors: MacKenzie
authors: Department of Biology, Dalhousie University, Canada.
authors: Collin
authors: C
authors: Ward
authors: Department of Biology, Dalhousie University, Canada.
authors: David
authors: D
authors: Salgado
authors: Department of Pathology, University California San Francisco, United States.
authors: Andrew
authors: A
authors: Leidal
authors: Department of Microbiology and Immunology, Dalhousie University, Canada.
authors: Craig
authors: C
authors: McCormick
authors: Department of Biology, Dalhousie University, Canada. Electronic address: bill.pohajdak@dal.ca.
authors: Bill
authors: B
authors: Pohajdak
mesh_terms: D015550:Cell Degranulation; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology / Q000502:physiology; D016764:Cell Polarity / Q000276:immunology / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D004268:DNA-Binding Proteins; D055785:Gene Knockdown Techniques; D006801:Humans; D007113:Immunity, Innate; D054992:Immunological Synapses / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000502:physiology*; D011554:Pseudopodia / Q000276:immunology / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D019718:Receptors, CXCR4 / Q000502:physiology; D014157:Transcription Factors
chemical_list: C527276:CXCR4 protein, human; C088424:Cux1 protein, rat; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; D014157:Transcription Factors; D007371:Interferon-gamma
keywords: CASP; Degranulation; Migration; NK cell; Polarization