scholarly journals GABAA Receptor Trafficking-Mediated Plasticity of Inhibitory Synapses

Neuron ◽  
2011 ◽  
Vol 70 (3) ◽  
pp. 385-409 ◽  
Author(s):  
Bernhard Luscher ◽  
Thomas Fuchs ◽  
Casey L. Kilpatrick
Keyword(s):  
Gabaa Receptor ◽  
Receptor Trafficking ◽  
Inhibitory Synapses

The role of GABAA receptor biogenesis, structure and function in epilepsy

2006 ◽  
Vol 34 (5) ◽  
pp. 863-867 ◽  
Author(s):  
S. Mizielinska ◽  
S. Greenwood ◽  
C.N. Connolly
Keyword(s):  
Gabaa Receptor ◽  
Structure And Function ◽  
Inhibitory Synapses ◽  
Normal Brain ◽  
Synaptic Targeting ◽  
Acid Type ◽  
Normal Brain Function ◽  
And Function ◽  
The Brain

Maintaining the correct balance in neuronal activation is of paramount importance to normal brain function. Imbalances due to changes in excitation or inhibition can lead to a variety of disorders ranging from the clinically extreme (e.g. epilepsy) to the more subtle (e.g. anxiety). In the brain, the most common inhibitory synapses are regulated by GABAA (γ-aminobutyric acid type A) receptors, a role commensurate with their importance as therapeutic targets. Remarkably, we still know relatively little about GABAA receptor biogenesis. Receptors are constructed as pentameric ion channels, with α and β subunits being the minimal requirement, and the incorporation of a γ subunit being necessary for benzodiazepine modulation and synaptic targeting. Insights have been provided by the discovery of several specific assembly signals within different GABAA receptor subunits. Moreover, a number of recent studies on GABAA receptor mutations associated with epilepsy have further enhanced our understanding of GABAA receptor biogenesis, structure and function.

Association of GRIP1 with a GABAA receptor associated protein suggests a role for GRIP1 at inhibitory synapses

2004 ◽  
Vol 68 (8) ◽  
pp. 1649-1654 ◽  
Author(s):  
Josef T. Kittler ◽  
I. Lorena Arancibia-Carcamo ◽  
Stephen J. Moss
Keyword(s):  
Gabaa Receptor ◽  
Inhibitory Synapses ◽  
Receptor Associated Protein

Benzodiazepine ligands rapidly influence GABAA receptor diffusion and clustering at hippocampal inhibitory synapses

2015 ◽  
Vol 88 ◽  
pp. 199-208 ◽  
Author(s):  
Sabine Lévi ◽  
Nicolas Le Roux ◽  
Emmanuel Eugène ◽  
Jean Christophe Poncer
Keyword(s):  
Gabaa Receptor ◽  
Inhibitory Synapses

scholarly journals The Clustering of GABAA Receptor Subtypes at Inhibitory Synapses is Facilitated via the Direct Binding of Receptor  2 Subunits to Gephyrin

2008 ◽  
Vol 28 (6) ◽  
pp. 1356-1365 ◽  
Author(s):  
V. Tretter ◽  
T. C. Jacob ◽  
J. Mukherjee ◽  
J.-M. Fritschy ◽  
M. N. Pangalos ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
Inhibitory Synapses ◽  
Receptor Subtypes ◽  
Direct Binding ◽  
Gabaa Receptor Subtypes

scholarly journals C-Terminal Modification Is Required for GABARAP-Mediated GABAA Receptor Trafficking

2007 ◽  
Vol 27 (25) ◽  
pp. 6655-6663 ◽  
Author(s):  
Z.-W. Chen ◽  
C.-S. S. Chang ◽  
T. A. Leil ◽  
R. W. Olsen
Keyword(s):  
Gabaa Receptor ◽  
Receptor Trafficking

scholarly journals Altered inhibitory synapses in de novo GABRA5 and GABRA1 mutations associated with early onset epileptic encephalopathies

Brain ◽  
2019 ◽  
Vol 142 (7) ◽  
pp. 1938-1954 ◽  
Author(s):  
Ciria C Hernandez ◽  
Wenshu XiangWei ◽  
Ningning Hu ◽  
Dingding Shen ◽  
Wangzhen Shen ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
Gabaa Receptors ◽  
Early Onset ◽  
De Novo ◽  
Epileptic Encephalopathy ◽  
Inhibitory Synapses ◽  
Causative Gene ◽  
Gabaergic Neurotransmission ◽  
Gaba Binding ◽  
Patients With Epilepsy

Abstract We performed next generation sequencing on 1696 patients with epilepsy and intellectual disability using a gene panel with 480 epilepsy-related genes including all GABAA receptor subunit genes (GABRs), and we identified six de novo GABR mutations, two novel GABRA5 mutations (c.880G>T, p.V294F and c.1238C>T, p.S413F), two novel GABRA1 mutations (c.778C>T, p.P260S and c.887T>C, p.L296S/c.944G>T, p.W315L) and two known GABRA1 mutations (c.335G>A, p.R112Q and c.343A>G, p.N115D) in six patients with intractable early onset epileptic encephalopathy. The α5(V294F and S413F) and α1(P260S and L296S/W315L) subunit residue substitutions were all in transmembrane domains, while the α1(R112Q and N115R) subunit residue substitutions were in the N-terminal GABA binding domain. Using multidisciplinary approaches, we compared effects of mutant GABAA receptor α5 and α1 subunits on the properties of recombinant α5β3γ2 and α1β3γ2 GABAA receptors in both neuronal and non-neuronal cells and characterized their effects on receptor clustering, biogenesis and channel function. GABAA receptors containing mutant α5 and α1 subunits all had reduced cell surface and total cell expression with altered endoplasmic reticulum processing, impaired synaptic clustering, reduced GABAA receptor function and decreased GABA binding potency. Our study identified GABRA5 as a causative gene for early onset epileptic encephalopathy and expands the mutant GABRA1 phenotypic spectrum, supporting growing evidence that defects in GABAergic neurotransmission contribute to early onset epileptic encephalopathy phenotypes.

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