Dynamin 2 regulates granule exocytosis during NK cell-mediated cytotoxicity.
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.
Arneson
Laura N
LN
Department of Immunology, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Segovis
Colin M
CM
Gomez
Timothy S
TS
Schoon
Renee A
RA
Dick
Christopher J
CJ
Lou
Zhenkun
Z
Billadeau
Daniel D
DD
Leibson
Paul J
PJ
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
D034285:Dynamin II