scholarly journals GABA receptor associated protein changes the electrostatic environment around the GABA type A receptor

2021 ◽  
Author(s):  
Benedict W. J. Irwin ◽  
Clara C. Wanjura ◽  
Daniel Molnar ◽  
Michael J. Rutter ◽  
Michael C. Payne ◽  
...  
Keyword(s):  
Gaba Receptor ◽  
Type A ◽  
Receptor Associated Protein

Identification of Clathrin Heavy Chain as a Direct Interaction Partner for the γ-Aminobutyric Acid Type A Receptor Associated Protein†

Biochemistry ◽  
2007 ◽  
Vol 46 (50) ◽  
pp. 14537-14543 ◽  
Author(s):  
Jeannine Mohrlüder ◽  
Yvonne Hoffmann ◽  
Thomas Stangler ◽  
Karen Hänel ◽  
Dieter Willbold
Keyword(s):  
Heavy Chain ◽  
Direct Interaction ◽  
Type A ◽  
Aminobutyric Acid ◽  
Interaction Partner ◽  
Receptor Associated Protein ◽  
Clathrin Heavy Chain ◽  
Acid Type

Structure and potential function of γ-aminobutyrate type A receptor-associated protein

FEBS Journal ◽  
2009 ◽  
Vol 276 (18) ◽  
pp. 4989-5005 ◽  
Author(s):  
Jeannine Mohrlüder ◽  
Melanie Schwarten ◽  
Dieter Willbold
Keyword(s):  
Potential Function ◽  
Type A ◽  
Receptor Associated Protein

Effects of Isoflurane on γ-Aminobutyric Acid Type A Receptors Activated by Full and Partial Agonists

2003 ◽  
Vol 98 (2) ◽  
pp. 306-311 ◽  
Author(s):  
Norbert Topf ◽  
Andrew Jenkins ◽  
Nicole Baron ◽  
Neil L. Harrison
Keyword(s):  
Gaba Receptor ◽  
Partial Agonist ◽  
Type A ◽  
Aminobutyric Acid ◽  
Hek293 Cells ◽  
Relative Efficacy ◽  
Gaba A ◽  
Mutant Receptor ◽  
Acid Type ◽  
Beta 2

Background Volatile anesthetics prolong inhibitory postsynaptic potentials in central neurons an allosteric action on the gamma-aminobutyric acid type A (GABA(A)) receptor, an effect that may underlie the hypnotic actions of these agents. Inhaled anesthetics such as isoflurane act to enhance responses to submaximal concentrations of GABA, but it is not clear whether their effect is mediated by an increase in the binding of the agonist or by changes in receptor gating behavior. To address this question, the authors studied the effects of isoflurane on a mutant GABA(A) receptor with a gating defect that decreases receptor sensitivity by lowering agonist efficacy. They then compared the effects of clinically relevant concentrations of isoflurane on the actions of GABA and piperidine-4-sulfonic acid (P4S), a partial agonist at the GABA(A) receptor. Methods The authors created a mutant of the GABA receptor alpha subunit (L277A) by site-directed mutagenesis. The mutant subunit was coexpressed with beta(2) and gamma(2S) subunits in HEK293 cells, and responses to GABA and P4S were recorded using the whole-cell patch clamp technique. EC values were determined for the full agonist GABA and the partial agonist P4S. The authors also determined the relative efficacy (epsilon) of P4S. These measurements were then repeated in the presence of isoflurane. Results The concentration-response curve for GABA was shifted to the right (EC(50) = 278 microm) in the alpha(1)(L277A)beta(2)gamma(2S) mutant receptor, compared with the corresponding wild-type alpha(1)beta(2)gamma(2S) GABA(A) receptor (EC(50) = 16 microm). P4S is a partial agonist at both receptors, with a dramatically decreased relative efficacy at the mutant receptor (epsilon = 0.24). When the mutant receptor was studied in the presence of isoflurane, the concentration-response curves for both GABA and P4S were shifted to the left (EC(50) for GABA = 78 microm); the efficacy of P4S also increased significantly (epsilon = 0.40). Conclusion By studying a mutant GABA receptor with impaired gating, the authors were able to demonstrate clearly that isoflurane can increase the efficacy of a partial agonist, as well as increase agonist potency. These data suggest that the volatile anesthetic isoflurane exerts at least some of its effects on the GABA(A) receptor via alterations in gating rather than simply changing binding or unbinding of the agonist.

scholarly journals Interaction of Calcineurin and Type-A GABA Receptor γ2Subunits Produces Long-Term Depression at CA1 Inhibitory Synapses

2003 ◽  
Vol 23 (3) ◽  
pp. 826-836 ◽  
Author(s):  
Jian Wang ◽  
ShuHong Liu ◽  
Ursula Haditsch ◽  
WeiHong Tu ◽  
Kimberley Cochrane ◽  
...  
Keyword(s):  
Gaba Receptor ◽  
Type A ◽  
Inhibitory Synapses ◽  
Long Term Depression

Therapeutically leveraging GABAA receptors in cancer

2021 ◽  
Vol 246 (19) ◽  
pp. 2128-2135
Author(s):  
Debanjan Bhattacharya ◽  
Vaibhavkumar S Gawali ◽  
Laura Kallay ◽  
Donatien K Toukam ◽  
Abigail Koehler ◽  
...  
Keyword(s):  
Gaba Receptors ◽  
Brain Function ◽  
Gaba Receptor ◽  
Krebs Cycle ◽  
Type A ◽  
Therapeutic Benefit ◽  
Disease States ◽  
The Central Nervous System ◽  
Pathological Disease ◽  
Gaba Receptor Subunits

γ-aminobutyric acid or GABA is an amino acid that functionally acts as a neurotransmitter and is critical to neurotransmission. GABA is also a metabolite in the Krebs cycle. It is therefore unsurprising that GABA and its receptors are also present outside of the central nervous system, including in immune cells. This observation suggests that GABAergic signaling impacts events beyond brain function and possibly human health beyond neurological disorders. Indeed, GABA receptor subunits are expressed in pathological disease states, including in disparate cancers. The role that GABA and its receptors may play in cancer development and progression remains unclear. If, however, those cancers have functional GABA receptors that participate in GABAergic signaling, it raises an important question whether these signaling pathways might be targetable for therapeutic benefit. Herein we summarize the effects of modulating Type-A GABA receptor signaling in various cancers and highlight how Type-A GABA receptors could emerge as a novel therapeutic target in cancer.

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