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.
Highlights
LEV-9 is an extracellular scaffolding protein required for synaptic clustering of acetylcholine receptors in C. elegans
At excitatory neuromuscular junctions (NMJs)3 in Caenorhabditis elegans, an extracellular scaffold containing the LEV-9 and LEV-10 proteins is required for levamisole-sensitive acetylcholine receptors (L-AChRs) clustering [6, 7]
We show that the lev-9 locus encodes multiple isoforms, including a long polypeptide containing 17 complement control protein (CCP) domains that is found in other species
Summary
Background: LEV-9 is an extracellular scaffolding protein required for synaptic clustering of acetylcholine receptors in C. elegans. Significance: Many LEV-9-related factors are likely cleaved after CCP domains, suggesting that cleavage location can be conserved in distant architecturally related proteins. 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.
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