AUTHOR=Zhou Xin , Bessereau Jean-Louis 

TITLE=Molecular Architecture of Genetically-Tractable GABA Synapses in C. elegans

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=12

YEAR=2019

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2019.00304

DOI=10.3389/fnmol.2019.00304

ISSN=1662-5099

ABSTRACT=<p>Inhibitory synapses represent a minority of the total chemical synapses in the mammalian brain, yet proper tuning of inhibition is fundamental to shape neuronal network properties. The neurotransmitter γ-aminobutyric acid (GABA) mediates rapid synaptic inhibition by the activation of the type A GABA receptor (GABA<sub>A</sub>R), a pentameric chloride channel that governs major inhibitory neuronal transduction in the nervous system. Impaired GABA transmission leads to a variety of neuropsychiatric diseases, including schizophrenia, autism, epilepsy or anxiety. From an evolutionary perspective, GABA<sub>A</sub>R shows remarkable conservations, and are found in all eukaryotic clades and even in bacteria and archaea. Specifically, <italic>bona fide</italic> GABA<sub>A</sub>Rs are found in the nematode <italic>Caenorhabditis elegans</italic>. Because of the anatomical simplicity of the nervous system and its amenability to genetic manipulations, <italic>C. elegans</italic> provide a powerful system to investigate the molecular and cellular biology of GABA synapses. In this mini review article, we will introduce the structure of the <italic>C. elegans</italic> GABAergic system and describe recent advances that have identified novel proteins controlling the localization of GABA<sub>A</sub>Rs at synapses. In particular, Ce-Punctin/MADD-4 is an evolutionarily-conserved extracellular matrix protein that behaves as an anterograde synaptic organizer to instruct the excitatory or inhibitory identity of postsynaptic domains.</p>