title: Dynamin 2 regulates granule exocytosis during NK cell-mediated cytotoxicity.
abstract: NK cells are innate immune cells that can eliminate their targets through granule release. In this study, we describe a specialized role for the large GTPase Dynamin 2 (Dyn2) in the regulation of these secretory events leading to cell-mediated cytotoxicity. By modulating the expression of Dyn2 using small interfering RNA or by inhibiting its activity using a pharmacological agent, we determined that Dyn2 does not regulate conjugate formation, proximal signaling, or granule polarization. In contrast, during cell-mediated killing, Dyn2 localizes with lytic granules and polarizes to the NK cell-target interface where it regulates the final fusion of lytic granules with the plasma membrane. These findings identify a novel role for Dyn2 in the exocytic events required for effective NK cell-mediated cytotoxicity.
authors.affiliation: Department of Immunology, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Laura N
authors.initials: LN
authors.lastname: Arneson
authors.forename: Colin M
authors.initials: CM
authors.lastname: Segovis
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Gomez
authors.forename: Renee A
authors.initials: RA
authors.lastname: Schoon
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Dick
authors.forename: Zhenkun
authors.initials: Z
authors.lastname: Lou
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Billadeau
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Leibson
mesh_terms: D003602:Cytotoxicity, Immunologic; D034285:Dynamin II / Q000276:immunology* / Q000378:metabolism; D005089:Exocytosis / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism; D021381:Protein Transport / Q000276:immunology; D022142:Secretory Vesicles / Q000276:immunology* / Q000378:metabolism
chemical_list: D034285:Dynamin II