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 journalArticle

24 Citations (Scopus)

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
StatePublished - Nov 15 2008

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Dynamin II
Exocytosis
Natural Killer Cells
GTP Phosphohydrolases
Small Interfering RNA
Cell Membrane
Pharmacology

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Arneson, L. N., Segovis, C. M., Gomez, T. S., Schoon, R. A., Dick, C. J., Lou, Z., ... Leibson, P. J. (2008). Dynamin 2 regulates granule exocytosis during NK cell-mediated cytotoxicity. Journal of Immunology, 181(10), 6995-7001.

Dynamin 2 regulates granule exocytosis during NK cell-mediated cytotoxicity. / Arneson, Laura N.; Segovis, Colin M.; Gomez, Timothy S.; Schoon, Renee A.; Dick, Christopher J.; Lou, Zhenkun; Billadeau, Daniel D; Leibson, Paul J.

In: Journal of Immunology, Vol. 181, No. 10, 15.11.2008, p. 6995-7001.

Research output: Contribution to journalArticle

Arneson, LN, Segovis, CM, Gomez, TS, Schoon, RA, Dick, CJ, Lou, Z, Billadeau, DD & Leibson, PJ 2008, 'Dynamin 2 regulates granule exocytosis during NK cell-mediated cytotoxicity', Journal of Immunology, vol. 181, no. 10, pp. 6995-7001.
Arneson LN, Segovis CM, Gomez TS, Schoon RA, Dick CJ, Lou Z et al. Dynamin 2 regulates granule exocytosis during NK cell-mediated cytotoxicity. Journal of Immunology. 2008 Nov 15;181(10):6995-7001.
Arneson, Laura N. ; Segovis, Colin M. ; Gomez, Timothy S. ; Schoon, Renee A. ; Dick, Christopher J. ; Lou, Zhenkun ; Billadeau, Daniel D ; Leibson, Paul J. / Dynamin 2 regulates granule exocytosis during NK cell-mediated cytotoxicity. In: Journal of Immunology. 2008 ; Vol. 181, No. 10. pp. 6995-7001.
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