Nitric oxide regulates exocytosis by S-nitrosylation of N-ethylmaleimide-sensitive factor.
Nitric oxide (NO) inhibits vascular inflammation, but the molecular basis for its anti-inflammatory properties is unknown. We show that NO inhibits exocytosis of Weibel-Palade bodies, endothelial granules that mediate vascular inflammation and thrombosis, by regulating the activity of N-ethylmaleimide-sensitive factor (NSF). NO inhibits NSF disassembly of soluble NSF attachment protein receptor (SNARE) complexes by nitrosylating critical cysteine residues of NSF. NO may regulate exocytosis in a variety of physiological processes, including vascular inflammation, neurotransmission, thrombosis, and cytotoxic T lymphocyte cell killing.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Kenji
K
Matsushita
Craig N
CN
Morrell
Beatrice
B
Cambien
Shui Xiang
SX
Yang
Munekazu
M
Yamakuchi
Clare
C
Bao
Makoto R
MR
Hara
Richard A
RA
Quick
Wangsen
W
Cao
Brian
B
O'Rourke
John M
JM
Lowenstein
Jonathan
J
Pevsner
Denisa D
DD
Wagner
Charles J
CJ
Lowenstein
D000818:Animals; D001011:Aorta / Q000166:cytology; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016297:Mutagenesis, Site-Directed; D052066:N-Ethylmaleimide-Sensitive Proteins; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism; D050600:SNARE Proteins; D013917:Thrombin / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D033921:Vesicular Transport Proteins; D020302:Weibel-Palade Bodies / Q000187:drug effects / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D002352:Carrier Proteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; D050600:SNARE Proteins; D042461:Vascular Endothelial Growth Factor A; D033921:Vesicular Transport Proteins; D014841:von Willebrand Factor; D009569:Nitric Oxide; D013917:Thrombin; D052066:N-Ethylmaleimide-Sensitive Proteins; C498733:Nsf protein, mouse; D003545:Cysteine; D019331:NG-Nitroarginine Methyl Ester