title: Proteolytic processing of the extracellular scaffolding protein LEV-9 is required for clustering acetylcholine receptors.
abstract: Correct positioning of neurotransmitter-gated receptors at postsynapses is essential for synaptic transmission. At Caenorhabditis elegans neuromuscular junctions, clustering of levamisole-sensitive acetylcholine receptors (L-AChRs) requires the muscle-secreted scaffolding protein LEV-9, a multidomain factor containing complement control protein (CCP) modules. Here we show that LEV-9 needs to be cleaved at its C terminus to exert its function. LEV-9 cleavage is not required for trafficking nor secretion but directly controls scaffolding activity. The cleavage site is evolutionarily conserved, and post-translational cleavage ensures the structural and functional decoupling between different isoforms encoded by the lev-9 gene. Data mining indicates that most human CCP-containing factors are likely cleaved C-terminally from CCP tandems, suggesting that not only domain architectures but also cleavage location can be conserved in distant architecturally related proteins.
authors.affiliation: Institute of Biology of Ecole Normale Supérieure, 75005 Paris,; INSERM, U1024, 75005 Paris,; Institut Jacques Monod UMR CNRS 7592, 75013 Paris, France. Electronic address: briseno-roa@ijm.univ-paris-diderot.fr.
authors.forename: Luis
authors.initials: L
authors.lastname: Briseño-Roa
authors.affiliation: Institute of Biology of Ecole Normale Supérieure, 75005 Paris,; INSERM, U1024, 75005 Paris,; University Claude Bernard Lyon 1, Centre de Génétique et de Physiologie Moléculaire et Cellulaire (CGphiMC) UMR CNRS 5534, 69622 Villeurbanne, and. Electronic address: jean-louis.bessereau@univ-lyon1.fr.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Bessereau
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D059748:Proteolysis; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; C545009:LEV-9 protein, C elegans; D020033:Protein Isoforms; D011950:Receptors, Cholinergic
keywords: CCP Domain; Extracellular Matrix Proteins; Limited Proteolysis; Nicotinic Acetylcholine Receptors; Post-translational Modification; Scaffold Proteins; Synapses