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 G'FPase 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. The Journal of Immunology, 2008, 181: 6995-7001.