Journal
SCIENCE SIGNALING
Volume 8, Issue 384, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.aaa4312
Keywords
-
Categories
Funding
- National Institute on Aging (NIA) [R01-AG13966]
- National Heart, Lung, and Blood Institute (NHLBI) [R01-HL054926]
- National Institute of Environmental Health Sciences (NIEHS) Center of Excellence in Environmental Toxicology [P30-ES013508]
- NIA training [T32-AG000255]
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [DK-053761]
- National Institute of Child Health and Human Development (NICHD) Intellectual and Developmental Disabilities Research Center (IDDRC) [P30-HD026979]
- National Institute of Neurological Disorders and Stroke (NINDS) training [T32-NS007413]
- NINDS [R01-NS077773]
Ask authors/readers for more resources
Nitric oxide (NO) is a signaling intermediate during glutamatergic neurotransmission in the central nervous system (CNS). NO signaling is in part accomplished through cysteine S-nitrosylation, a posttranslational modification by which NO regulates protein function and signaling. In our investigation of the protein targets and functional impact of S-nitrosylation in the CNS under physiological conditions, we identified 269 S-nitrosocysteine residues in 136 proteins in the wild-type mouse brain. The number of sites was significantly reduced in the brains of mice lacking endothelial nitric oxide synthase (eNOS(-/-)) or neuronal nitric oxide synthase (nNOS(-/-)). In particular, nNOS(-/-) animals showed decreased S-nitrosylation of proteins that participate in the glutamate/glutamine cycle, a metabolic process by which synaptic glutamate is recycled or oxidized to provide energy. N-15-glutamine-based metabolomic profiling and enzymatic activity assays indicated that brain extracts from nNOS(-/-) mice converted less glutamate to glutamine and oxidized more glutamate than those from mice of the other genotypes. GLT1 [also known as EAAT2 (excitatory amino acid transporter 2)], a glutamate transporter in astrocytes, was S-nitrosylated at Cys(373) and Cys(561) in wild-type and eNOS-/- mice, but not in nNOS-/- mice. A form of rat GLT1 that could not be S-nitrosylated at the equivalent sites had increased glutamate uptake compared to wild-type GLT1 in cells exposed to an S-nitrosylating agent. Thus, NO modulates glutamatergic neurotransmission through the selective, nNOS-dependent S-nitrosylation of proteins that govern glutamate transport and metabolism.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available