A single immunoglobulin-domain protein required for clustering acetylcholine receptors in C. elegans.
At Caenorhabditis elegans neuromuscular junctions (NMJs), synaptic clustering of the levamisole-sensitive acetylcholine receptors (L-AChRs) relies on an extracellular scaffold assembled in the synaptic cleft. It involves the secreted protein LEV-9 and the ectodomain of the transmembrane protein LEV-10, which are both expressed by muscle cells. L-AChRs, LEV-9 and LEV-10 are part of a physical complex, which localizes at NMJs, yet none of its components localizes independently at synapses. In a screen for mutants partially resistant to the cholinergic agonist levamisole, we identified oig-4, which encodes a small protein containing a single immunoglobulin domain. The OIG-4 protein is secreted by muscle cells and physically interacts with the L-AChR/LEV-9/LEV-10 complex. Removal of OIG-4 destabilizes the complex and causes a loss of L-AChR clusters at the synapse. Interestingly, OIG-4 partially localizes at NMJs independently of LEV-9 and LEV-10, thus providing a potential link between the L-AChR-associated scaffold and local synaptic cues. These results add a novel paradigm for the immunoglobulin super-family as OIG-4 is a secreted protein required for clustering ionotropic receptors independently of synapse formation.
Biology Department, Ecole Normale Supérieure, IBENS, Paris, France.
Georgia
G
Rapti
Janet
J
Richmond
Jean-Louis
JL
Bessereau
D000818:Animals; D030801:Animals, Genetically Modified; D000871:Anthelmintics / Q000494:pharmacology; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018679:Cholinergic Agonists / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D007136:Immunoglobulins / Q000737:chemistry; D007978:Levamisole / Q000494:pharmacology; D008954:Models, Biological; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
D000871:Anthelmintics; D029742:Caenorhabditis elegans Proteins; D018679:Cholinergic Agonists; D007136:Immunoglobulins; D011950:Receptors, Cholinergic; D007978:Levamisole
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