+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Demonstration of functional coupling between gamma -aminobutyric acid (GABA) synthesis and vesicular GABA transport into synaptic vesicles



Demonstration of functional coupling between gamma -aminobutyric acid (GABA) synthesis and vesicular GABA transport into synaptic vesicles



Proceedings of the National Academy of Sciences of the United States of America 100(7): 4293-4298



l-Glutamic acid decarboxylase (GAD) exists as both membrane-associated and soluble forms in the mammalian brain. Here, we propose that there is a functional and structural coupling between the synthesis of gamma-aminobutyric acid (GABA) by membrane-associated GAD and its packaging into synaptic vesicles (SVs) by vesicular GABA transporter (VGAT). This notion is supported by the following observations. First, newly synthesized [(3)H]GABA from [(3)H]l-glutamate by membrane-associated GAD is taken up preferentially over preexisting GABA by using immunoaffinity-purified GABAergic SVs. Second, the activity of SV-associated GAD and VGAT seems to be coupled because inhibition of GAD also decreases VGAT activity. Third, VGAT and SV-associated Ca(2+)calmodulin-dependent kinase II have been found to form a protein complex with GAD. A model is also proposed to link the neuronal stimulation to enhanced synthesis and packaging of GABA into SVs.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 048730573

Download citation: RISBibTeXText

PMID: 12634427

DOI: 10.1073/pnas.0730698100


Related references

Demonstration of functional coupling between c-aminobutyric (GABA) synthesis and vesicular GABA transport into synaptic vesicles. Proceedings of the National Academy of Sciences of the United States of America 100(7): 93-8, 2003

Demonstration of coupling between GABA synthesis and vesicular GABA transport in synaptic vesicles. Society for Neuroscience Abstracts 27(1): 25, 2001

Gamma-Aminobutyric acid (GABA) signaling components in Drosophila: immunocytochemical localization of GABA(B) receptors in relation to the GABA(A) receptor subunit RDL and a vesicular GABA transporter. Journal of Comparative Neurology 505(1): 18-31, 2007

Gamma aminobutyric acid gaba uptake into synaptic vesicles. Journal of Neurochemistry 48(Suppl.): S73, 1987

Neurochemical studies on gamma aminobutyric acid gaba receptor xxii. functional coupling of cerebral gaba b receptor with adenylate cyclase system. Japanese Journal of Pharmacology 46(Suppl.): 203P, 1988

The physiological significance of gamma-aminobutyric acid (GABA) in brain function. I. The pharmacological similarity of alpha-chloro-gamma-aminobutyric acid (alpha-CI-GABA) to gamma-aminobutyric acid (GABA). Nihon Seirigaku Zasshi. Journal of the Physiological Society of Japan 30(2): 109-113, 1968

Functional coupling of gamma-aminobutyric acid (GABA)A and benzodiazepine type II receptors: analysis using purified GABA/benzodiazepine receptor complex from bovine cerebral cortex. Neuropharmacology 26(12): 1745-1750, 1987

Effect of thyrotropin releasing hormone (TRH) on GABA (gamma aminobutyric acid) metabolism in mouse and rat brains: as to the activities of GAD (glutamic acid decarboxylase), GABA-T (GABA-transaminase) and GABA re-uptake. No to Shinkei 37(12): 1211-1216, 1985

Synthesis and proton NMR spectroscopy of intra-vesicular gamma-aminobutyric acid (GABA). Conference Proceedings 2013: 1093-1095, 2013

Activity-dependent enhancement of hyperpolarizing and depolarizing gamma-aminobutyric acid (GABA) synaptic responses following inhibition of GABA uptake by tiagabine. Epilepsy Research 37(1): 25-36, 1999

Enantioselective synthesis of s gamma acetylenic gamma aminobutyric acid gaba and s trans gamma butenynyl gaba. Journal of the Chemical Society Chemical Communications (15): 1025-1027, 1989

Regulation of transmitter gamma-aminobutyric acid (GABA) synthesis and metabolism illustrated by the effect of gamma-vinyl GABA and hypoglycemia. Journal of Neurochemistry 50(4): 1151-1157, 1988

Levels of total gamma-aminobutyric acid (GABA), free GABA and homocarnosine in cerebrospinal fluid of epileptic patients before and during gamma-vinyl-GABA (vigabatrin) treatment. Journal of the Neurological Sciences 88(1-3): 83-93, 1988

A study of the uptake of glutamate, gamma-aminobutyric acid (GABA), glycine and beta-alanine in synaptic brain vesicles from fish and avians. Neuroscience Letters 183(1-2): 62-66, 1995

Synaptic membrane transport of choline and of gamma aminobutyric acid gaba effects of ethanol and other n alcohols. Neurotoxicology (little Rock): 689, 1988