Thioredoxin increases exocytosis by denitrosylating N-ethylmaleimide- sensitive factor

Takashi Ito, Munekazu Yamakuchi, Charles J. Lowenstein

Research output: Contribution to journalArticlepeer-review

Abstract

Exocytosis involves membrane fusion between granules and the plasma membrane. Nitric oxide (NO) inhibits exocytosis by chemically modifying N-ethylmaleimide-sensitive factor (NSF), a key component of the exocytic machinery. However, cells recover the ability to release messenger molecules within hours of exposure to NO through unknown mechanisms. We now identify thioredoxin (TRX1) as a denitrosylase that reverses NO inhibition of exocytosis. Endogenously synthesized NO increases S-nitrosylated NSF levels, but S-nitrosylated NSF levels decrease within 3 h after exposure to NO. We found that NO increases the interaction between TRX1 and NSF, and endogenous TRX1 removes NO from S-nitrosylated NSF. Knockdown of TRX1 increases the level of S-nitrosylated NSF, prolongs the inhibition of exocytosis, and suppresses leukocyte adhesion. Taken together, these data show thatTRX1promotes exocytosis by denitrosylating NSF. Our findings suggest that TRX1 might regulate exocytosis in a variety of physiological settings, such as vascular inflammation, thrombosis, and insulin release.

Original languageEnglish (US)
Pages (from-to)11179-11184
Number of pages6
JournalJournal of Biological Chemistry
Volume286
Issue number13
DOIs
StatePublished - Apr 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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