+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Glutamic acid decarboxylases and GABA transporters determine GABA trafficking and function



Glutamic acid decarboxylases and GABA transporters determine GABA trafficking and function



Society for Neuroscience Abstracts 27(2): 1838



We hypothesize that together, GABA-synthesizing and GABA-transporting molecules determine GABA location, which is fundamental to its role. Two glutamic acid decarboxylases (GADs) synthesize GABA. We believe that GAD65 makes GABA that is packaged by the vesicular GABA transporter (vGAT) for exocytotic release. GAD67, found throughout the cytosol, produces cytosolic GABA, which can exit the cell via the plasma membrane GABA transporter (GAT). Exocytotically released GABA results in high synaptic concentrations for brief time periods. GAT-mediated GABA release may have different spatial and temporal constraints. High-sensitivity GABA detectors may elucidate these differences. We designed cDNA constructs with GAD65, GAD67, vGAT or GAT fused to color variants of GFP. Transient transfection of our constructs into fibroblast and neural cells yields proteins detectable by fluorescent microscopy. GAD-transfected cells produce enzymatically active GADs and micromoles of GABA. We can stimulate exocytotic or carrier-mediated GABA release and determine how GAD67-synthesized vs. GAD65-synthesized GABA exits the cell. We quantified GABA by HPLC, but this technique lacks the resolution required to distinguish vesicular and paracrine GABA release. We are designing sol-gel monolith and fiber-optic GABA sensors based on our glutamate sensors that detect uM to mM glutamate over seconds. Monolith sensors measure time-resolved release from cell populations. Fiber-optic sensors provide spatial as well as temporal information.

(PDF emailed within 1 workday: $29.90)

Accession: 034998015

Download citation: RISBibTeXText


Related references

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

GABA and pancreatic b-cells: colocalization of glutamic acid decarboxylase (GAD) and GABA with synaptic-like microvesicles suggests their role in GABA storage and secretion. The EMBO Journal 10: 75-84, 1991

GABA and pancreatic beta-cells: colocalization of glutamic acid decarboxylase (GAD) and GABA with synaptic-like microvesicles suggests their role in GABA storage and secretion. Embo Journal 10(5): 1275-1284, 1991

Analysis of the messenger RNA of glutamic acid decarboxylases , gamma-aminobutyric acid A receptors, and GABA transporter in the hippocampus of Ihara epileptic rat Quantitative RT-PCR and in situ hybridization studies. Epilepsia 42(Supplement 6): 69, 2001

The GABA(B2) subunit is critical for the trafficking and function of native GABA(B) receptors. Biochemical Pharmacology 68(8): 1655-1666, 2004

Hepatic encephalopathy in cirrhotic and portacaval shunted dogs lack of changes in brain gaba uptake brain gaba levels brain glutamic acid decarboxylase activity and brain postsynaptic gaba receptors. Hepatology 8(4): 845-849, 1988

Regulation of gamma-aminobutyric acid (GABA) transporters by extracellular GABA. Journal of Biological Chemistry 274(2): 889-895, 1999

Gamma-vinyl GABA increases nonvesicular release of GABA and glutamate in the nucleus accumbens in rats via action on anion channels and GABA transporters. Psychopharmacology 208(4): 511-519, 2011

The effects of in vivo inactivation of GABA-transaminase and glutamic acid decarboxylase on levels of GABA in the rat retina. Brain Research 419(1-2): 208-215, 1987

Role of nitric oxide on GABA, glutamic acid, activities of GABA-T and GAD in rat brain cerebral cortex. Brain Research 837(1-2): 229-235, Aug 7, 1999

Regulation of c-aminobutyric acid (GABA) transporters by extracellular GABA. The Journal of Biological Chemistry 274(2): 9-95, 1999

GABA, glutamic acid decarboxylase, and GABA transaminase levels in the myenteric plexus in the intestine of humans and other mammals. Journal of Neurochemistry 40(3): 861-865, 1983

Five-membered N-heterocyclic Scaffolds as Novel Amino Bioisosteres at -Aminobutyric Acid (GABA) Type A Receptors and GABA Transporters. Journal of Medicinal Chemistry 2019, 2019

The role of N-glycosylation in the stability, trafficking and GABA-uptake of GABA-transporter 1. Terminal N-glycans facilitate efficient GABA-uptake activity of the GABA transporter. Febs Journal 272(7): 1625-1638, 2005

Molecular heterogeneity of the c-aminobutyric acid (GABA) transport system. Cloning of two novel high affinity GABA transporters from rat brain. The Journal of Biological Chemistry 267: 098-104, 1992