GABA is dispensable for the formation of junctional GABA receptor clusters in Caenorhabditis elegans.
At GABAergic synapses, GABA receptors form high-density clusters opposite GABA release sites. Whether GABA release per se plays a role in the formation of GABA receptor clusters remains uncertain. To address this question in vivo, we characterized GABA receptor clustering in the nematode Caenorhabditis elegans. In C. elegans, body wall muscles receive excitatory inputs from cholinergic motor neurons and inhibitory inputs from GABAergic neurons. Using immunohistochemistry and green fluorescent protein-tagged proteins, we observed that the muscle GABA receptor UNC-49 is precisely clustered opposite GABA release sites. During development, these clusters appear slightly after the detection of presynaptic vesicles. If motor axons are mislocalized as in unc-5 mutants, GABA receptors cluster opposite ectopic axons at GABA release sites. Together, these data imply that a motor neuron-derived factor is instructing GABA receptor clustering. Presynaptic localization of this clustering activity requires the neuronal kinesin UNC-104, suggesting that release of GABA from synaptic vesicles may represent the clustering signal. However, unc-25 mutants do not synthesize GABA but do cluster postsynaptic GABA receptors indistinguishably from the wild type. Therefore, at GABAergic neuromuscular junctions, GABA receptor clustering requires nerve-muscle interaction but not GABA neurotransmission.
Gally
Christelle
C
Laboratoire de Biologie Cellulaire de la Synapse Normale et Pathologique, Institut National de la Santé et de la Recherche Médicale, Unité 497, Ecole Normale Supérieure, 75005 Paris, France.
Bessereau
Jean-Louis
JL
D000818:Animals; D017173:Caenorhabditis elegans / Q000737:chemistry* / Q000166:cytology / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins; D002454:Cell Differentiation; D016547:Kinesins / Q000502:physiology; D007700:Kinetics; D009046:Motor Neurons / Q000502:physiology; D009132:Muscles / Q000294:innervation; D009419:Nerve Tissue Proteins / Q000502:physiology; D009469:Neuromuscular Junction / Q000737:chemistry* / Q000254:growth & development / Q000502:physiology / Q000648:ultrastructure; D021381:Protein Transport; D018079:Receptors, GABA / Q000032:analysis*; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D009419:Nerve Tissue Proteins; D018079:Receptors, GABA; C423186:UNC-104 protein, C elegans; D005680:gamma-Aminobutyric Acid; D016547:Kinesins