title: IQGAP1 involvement in MTOC and granule polarization in NK-cell cytotoxicity.
abstract: Natural killer (NK) cells form a region of tight contact called the NK immunological synapse (NKIS) with their target cells. This is a dynamic region serving as a platform for targeted signaling and exocytotic events. We previously identified IQGAP1 as a cytoskeletal component of the NK-like cell line YTS. The present study was undertaken to determine the role of IQGAP1 in the function of NK cells. Silencing of IQGAP1 expression resulted in almost complete loss of the cytotoxic activity of YTS cells. Loss of IQGAP1 did not prevent conjugate formation with target cells but it did result in a failure to reorient the microtubule organizing centre to the immune synapse. Significantly, IQGAP1 expression was required for the perigranular accumulation of an F-actin network. IQGAP1 was shown to undergo marked rearrangements during synapse maturation in effector target conjugates of YTS or primary NK cells. These results suggest previously undescribed role(s) for IQGAP1 in regulating multiple aspects of cytoskeletal organization and granule polarization in NK cells.
authors.affiliation: Manitoba Centre for Proteomics and Systems Biology, Winnipeg, Manitoba, Canada. kanwar@cc.umanitoba.ca
authors.forename: Namita
authors.initials: N
authors.lastname: Kanwar
authors.forename: John A
authors.initials: JA
authors.lastname: Wilkins
mesh_terms: D000199:Actins / Q000378:metabolism*; D045744:Cell Line, Tumor; D016764:Cell Polarity / Q000235:genetics; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D006801:Humans; D054992:Immunological Synapses / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D022101:Microtubule-Organizing Center / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D022142:Secretory Vesicles / Q000648:ultrastructure*; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D000199:Actins; C101203:IQ motif containing GTPase activating protein 1; D034741:RNA, Small Interfering; D020703:ras GTPase-Activating Proteins