A Mutated Acetylcholine Receptor Subunit Causes Neuronal Degeneration in C. Elegans

Neuron. 1995 Apr;14(4):871-7. doi: 10.1016/0896-6273(95)90231-7.

Abstract

Neurotoxicity through abnormal activation of membrane channels is a potential cause of neurodegenerative disease. Here we show that a gain-of-function mutation, deg.3(u662), leads to the degeneration of a small set of neurons in the nematode C. elegans. The deg.3 gene encodes a nicotinic acetylcholine receptor alpha subunit, which in the region of transmembrane domain II is most similar to the neuronal alpha 7 subunits from rat and chicken. The u662 mutation changes a residue in the second transmembrane domain, the domain thought to form the channel pore. A similar change in the equivalent amino acid in the chick protein produces channels that desensitize slowly. Channel hyperactivity may underlie the degenerations seen in the C. elegans deg.3(u662) mutants, since antagonists of nicotinic acetylcholine receptors suppress the deg-3(u662) mutant phenotypes.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Caenorhabditis / genetics
  • Caenorhabditis / physiology*
  • Gene Expression
  • Green Fluorescent Proteins
  • Luminescent Proteins / genetics
  • Macromolecular Substances
  • Molecular Sequence Data
  • Mutation*
  • Nerve Degeneration*
  • Nicotine / antagonists & inhibitors
  • Phenotype
  • Receptors, Cholinergic / chemistry*
  • Receptors, Cholinergic / genetics
  • Receptors, Cholinergic / physiology*
  • Recombinant Fusion Proteins
  • Restriction Mapping

Substances

  • Luminescent Proteins
  • Macromolecular Substances
  • Receptors, Cholinergic
  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins
  • Nicotine

Associated data

  • GENBANK/U19746
  • GENBANK/U19747