A mutated acetylcholine receptor subunit causes neuronal degeneration in C. elegans

Abstract

AbstractNeurotoxicity 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 α subunit, which in the region of transmembrane domain II is most similar to the neuronal α7 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 deg3(u662) mutant phenotypes