TY - JOUR
T1 - Dynamin 2 regulates granule exocytosis during NK cell-mediated cytotoxicity
AU - Arneson, Laura N.
AU - Segovis, Colin M.
AU - Gomez, Timothy S.
AU - Schoon, Renee A.
AU - Dick, Christopher J.
AU - Lou, Zhenkun
AU - Billadeau, Daniel D.
AU - Leibson, Paul J.
PY - 2008/11/15
Y1 - 2008/11/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.181.10.6995
DO - 10.4049/jimmunol.181.10.6995
M3 - Article
C2 - 18981119
AN - SCOPUS:58149198192
SN - 0022-1767
VL - 181
SP - 6995
EP - 7001
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -