Dynamin 2 regulates granule exocytosis during NK cell-mediated cytotoxicity

Laura N. Arneson, Colin M. Segovis, Timothy S. Gomez, Renee A. Schoon, Christopher J. Dick, Zhenkun Lou, Daniel D. Billadeau, Paul J. Leibson

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6995-7001
Number of pages7
JournalJournal of Immunology
Volume181
Issue number10
DOIs
StatePublished - Nov 15 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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