The
ric-3 mutation was isolated via two separate screens: for suppressors of the neuronal degeneration caused by the mutated nicotinic acetylcholine receptor (nAChR) subunit
deg-3(
u662) 1 , and in a screen for mutants resistant to the acetylcholinesterase inhibitor aldicarb 2 . As the
ric-3 mutants do not show reduced levels of acetylcholine and are resistant to the nAChR agonist levamisole, the aldicarb resistance is likely to originate with a defect in postsynaptic transmission. The specificity of the
ric-3 mutation to cholinergic signalling is indicated by study of the slow pharyngeal pumping observed in
ric-3 mutants. Electropharyngeograms (EPGs) of
ric-3 mutants show that while the glutamergic M3 spikes are unaffected, the cholinergic MC spike is absent. The defect in the MC spike is more severe in the
ric-3 mutants than in mutants lacking the pharyngeal nAChR subunits EAT-2 or EAT-18, suggesting that
ric-3 may affect the muscarinic AChR as well. The association of
ric-3 with the function of such heterogenous acetylcholine receptors as the levamisole receptor, the pharyngeal nAChRs, and DEG-3, which is evolutionarily ancient, suggests that
ric-3 does not code for an nAChR subunit. We are in the process of cloning
ric-3 via transposon tagging and cosmid transformation rescue, having been fortunate in receiving a set of
ric-3 alleles, including transposon insertion alleles, from James Rand. Ric-3 maps between
unc-8 and
unc-24 on chromosome IV. We think it of great interest to discover how RIC-3 acts as a general modulator of acetylcholine receptor function. RIC-3 may be involved in receptor synthesis, targetting or clustering, or may be a factor which alters regulation of the channel via postranslational modifications. 1.Treinin, M. and M. Chalfie (1995). Neuron 14, 871-877. 2. Miller, K. G. et al . (1996). Proc. Natl. Acad. Sci. USA 93, 12593-12598.