Characterization of the deg-3/des-2 receptor: a nicotinic acetylcholine receptor that mutates to cause neuronal degeneration

Mol Cell Neurosci. 2001 Mar;17(3):589-99. doi: 10.1006/mcne.2000.0944.

Abstract

The nicotinic acetylcholine receptor family (nAChR) is a large family of acetylcholine-gated cation channels. Here we characterize the Caenorhabditis elegans DEG-3/DES-2 nAChR, a receptor identified due to its involvement in neuronal degeneration. Pharmacological analysis of a DEG-3/DES-2 receptor expressed in Xenopus oocytes shows that this receptor is preferentially activated by choline. This choline sensitivity of the DEG-3/DES-2 channel can explain its role in neuronal degeneration, as shown by the toxic effects of choline on oocytes expressing the mutant DEG-3/DES-2 channel. We also show that in C. elegans the DEG-3/DES-2 receptor is localized to nonsynaptic regions, including the sensory endings of chemosensory neurons. This localization is in agreement with a role for this receptor in chemosensation of choline, as inferred from a defect in chemotaxis for choline seen in deg-3 mutants. Thus, this work also provides evidence for the diversity of nonsynaptic activities associated with nAChRs.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans
  • Calcium / metabolism
  • Chelating Agents / pharmacology
  • Chemotaxis / physiology
  • Choline / toxicity
  • Egtazic Acid / pharmacology
  • Electrophysiology
  • Molecular Sequence Data
  • Mutation / physiology
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / physiopathology*
  • Neurons, Afferent / cytology
  • Neurons, Afferent / physiology
  • Nootropic Agents / toxicity
  • Oocytes / physiology
  • Receptors, Nicotinic / analysis
  • Receptors, Nicotinic / genetics*
  • Receptors, Nicotinic / metabolism*
  • Synapses / chemistry
  • Xenopus

Substances

  • Chelating Agents
  • Nootropic Agents
  • Receptors, Nicotinic
  • Egtazic Acid
  • Choline
  • Calcium