title: C. elegans Punctin Clusters GABA(A) Receptors via Neuroligin Binding and UNC-40/DCC Recruitment.
abstract: Positioning type A GABA receptors (GABA(A)Rs) in front of GABA release sites sets the strength of inhibitory synapses. The evolutionarily conserved Ce-Punctin/MADD-4 is an anterograde synaptic organizer that specifies GABAergic versus cholinergic identity of postsynaptic domains at the C. elegans neuromuscular junctions (NMJs). Here we show that the Ce-Punctin secreted by GABAergic motor neurons controls the clustering of GABA(A)Rs through the synaptic adhesion molecule neuroligin (NLG-1) and the netrin receptor UNC-40/DCC. The short isoform of Ce-Punctin binds and clusters NLG-1 postsynaptically at GABAergic NMJs. NLG-1 disruption causes a strong reduction of GABA(A)R content at GABAergic synapses. Ce-Punctin also binds and localizes UNC-40 receptors in the postsynaptic membrane of NMJs, which promotes the recruitment of GABA(A)Rs by NLG-1. Since the mammalian orthologs of these genes are expressed in the central nervous system and their mutations are implicated in neuropsychiatric diseases, this molecular pathway might have been evolutionarily conserved.
authors.affiliation: University Claude Bernard Lyon1, CGphiMC UMR CNRS 5534, 69622 Villeurbanne, France.
authors.forename: Haijun
authors.initials: H
authors.lastname: Tu
authors.affiliation: University Claude Bernard Lyon1, CGphiMC UMR CNRS 5534, 69622 Villeurbanne, France.
authors.forename: Bérangère
authors.initials: B
authors.lastname: Pinan-Lucarré
authors.affiliation: University Claude Bernard Lyon1, CGphiMC UMR CNRS 5534, 69622 Villeurbanne, France.
authors.forename: Tingting
authors.initials: T
authors.lastname: Ji
authors.affiliation: University Claude Bernard Lyon1, CGphiMC UMR CNRS 5534, 69622 Villeurbanne, France.
authors.forename: Maelle
authors.initials: M
authors.lastname: Jospin
authors.affiliation: University Claude Bernard Lyon1, CGphiMC UMR CNRS 5534, 69622 Villeurbanne, France. Electronic address: jean-louis.bessereau@univ-lyon1.fr.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Bessereau
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D004558:Electric Stimulation; D059330:GABAergic Neurons / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D032342:Muscle Cells / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D008164:Luminescent Proteins; C568399:MADD-4 protein, C elegans; D009419:Nerve Tissue Proteins; D011963:Receptors, GABA-A; D025521:Tumor Suppressor Proteins; C102174:UNC-40 protein, C elegans; C093438:neuroligin 1