A transmembrane protein required for acetylcholine receptor clustering in Caenorhabditis elegans

Nature. 2004 Sep 30;431(7008):578-82. doi: 10.1038/nature02893.


Clustering neurotransmitter receptors at the synapse is crucial for efficient neurotransmission. Here we identify a Caenorhabditis elegans locus, lev-10, required for postsynaptic aggregation of ionotropic acetylcholine receptors (AChRs). lev-10 mutants were identified on the basis of weak resistance to the anthelminthic drug levamisole, a nematode-specific cholinergic agonist that activates AChRs present at neuromuscular junctions (NMJs) resulting in muscle hypercontraction and death at high concentrations. In lev-10 mutants, the density of levamisole-sensitive AChRs at NMJs is markedly reduced, yet the number of functional AChRs present at the muscle cell surface remains unchanged. LEV-10 is a transmembrane protein localized to cholinergic NMJs and required in body-wall muscles for AChR clustering. We also show that the LEV-10 extracellular region, containing five predicted CUB domains and one LDLa domain, is sufficient to rescue AChR aggregation in lev-10 mutants. This suggests a mechanism for AChR clustering that relies on extracellular protein-protein interactions. Such a mechanism is likely to be evolutionarily conserved because CUB/LDL transmembrane proteins similar to LEV-10, but lacking any assigned function, are expressed in the mammalian nervous system and might be used to cluster ionotropic receptors in vertebrates.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antinematodal Agents / pharmacology
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Carrier Proteins / metabolism
  • Cloning, Molecular
  • Dose-Response Relationship, Drug
  • Drug Resistance / drug effects
  • Exons / genetics
  • Gene Expression Regulation
  • Levamisole / pharmacology
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Motor Neurons / drug effects
  • Motor Neurons / metabolism
  • Mutation / genetics
  • Phenotype
  • Protein Structure, Tertiary
  • Protein Transport
  • Receptors, Cholinergic / metabolism*
  • Synapses / metabolism
  • Vesicular Acetylcholine Transport Proteins
  • Vesicular Transport Proteins*


  • Antinematodal Agents
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • LEV-10 protein, C elegans
  • Membrane Proteins
  • Receptors, Cholinergic
  • Unc-17 protein, C elegans
  • Vesicular Acetylcholine Transport Proteins
  • Vesicular Transport Proteins
  • Levamisole

Associated data

  • GENBANK/BN000434
  • GENBANK/BN000435