GluD1 binds GABA and controls inhibitory plasticity
Laura Piot1, Christina Heroven2, Simon Bossi1
1Institut de Biologie de l'ENS (IBENS), Ecole Normale Supérieure, Université PSL, CNRS, INSERM, F-75005 Paris, France.
Science (New York, N.Y.)
|December 7, 2023
Summary
The GluD1 receptor, an ionotropic glutamate receptor, binds GABA and enhances inhibitory neurotransmission in the hippocampus. This finding challenges the traditional view of distinct glutamatergic and GABAergic receptor functions.
Area of Science:
- Neuroscience
- Synaptic Plasticity
- Molecular Biology
Background:
- Fast synaptic transmission relies on ionotropic glutamate receptors (iGluRs) for excitation and GABAARs for inhibition.
- The iGluR family member GluD1 is found at both excitatory and inhibitory synapses, but its role in inhibition is unknown.
Purpose of the Study:
- To investigate the function of the GluD1 receptor in inhibitory neurotransmission.
- To determine if GluD1 activation affects GABAergic signaling.
Main Methods:
- Biochemical analyses
- Structural analyses
- Functional analyses
- Electrophysiology in adult mouse hippocampus
Main Results:
- GluD1 binds to GABA, a novel function for iGluRs.
- GluD1 activation enhances GABAergic synaptic currents via a non-ionotropic mechanism.
- This enhancement is dependent on trans-synaptic anchoring.
Conclusions:
- GluD1 acts as a GABA receptor, modulating inhibitory synaptic plasticity.
- This discovery challenges the classical separation of glutamatergic and GABAergic receptor roles.
Related Concept Videos
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.3K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.3K
01:12GPCR Desensitization
6.1K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
6.1K
01:19Ligand-gated Ion Channels
12.4K
Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
12.4K
01:09GPCRs Regulate Adenylyl Cylase Activity
5.6K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.6K
01:22Activation and Inactivation of G Proteins
7.2K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
7.2K
01:18Antiepileptic Drugs: GABAergic Pathway Potentiators
413
γ-aminobutyric acid or GABA, plays a pivotal role as an inhibitory neurotransmitter in the brain. GABA pathway potentiators, also known as GABAergic drugs, are a class of pharmaceutical agents designed to enhance the functioning of the GABAergic system. These medications primarily treat epilepsy, a neurological disorder characterized by recurrent seizures.
The key GABA pathway potentiators used in epilepsy management are as follows.
Benzodiazepines are a well-known class of drugs used for...
The key GABA pathway potentiators used in epilepsy management are as follows.
Benzodiazepines are a well-known class of drugs used for...
413