Characterization of the deg-3/des-2 receptor: a nicotinic acetylcholine receptor that mutates to cause neuronal degeneration.
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.
Yassin
L
L
Department of Physiology, Hadassah Medical School, Jerusalem, 91120, Israel.
Gillo
B
B
Kahan
T
T
Halevi
S
S
Eshel
M
M
Treinin
M
M
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D002633:Chemotaxis / Q000502:physiology; D002794:Choline / Q000633:toxicity; D004533:Egtazic Acid / Q000494:pharmacology; D004594:Electrophysiology; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D009475:Neurons, Afferent / Q000166:cytology / Q000502:physiology; D018697:Nootropic Agents / Q000633:toxicity; D009865:Oocytes / Q000502:physiology; D011978:Receptors, Nicotinic / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D013569:Synapses / Q000737:chemistry; D014981:Xenopus
D002614:Chelating Agents; D018697:Nootropic Agents; D011978:Receptors, Nicotinic; D004533:Egtazic Acid; D002794:Choline; D002118:Calcium