Dynamin 2 regulates granule exocytosis during NK cell-mediated cytotoxicity |
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Authors: | Arneson Laura N Segovis Colin M Gomez Timothy S Schoon Renee A Dick Christopher J Lou Zhenkun Billadeau Daniel D Leibson Paul J |
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Institution: | Department of Immunology, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA. |
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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. |
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