CGC Bibliography Paper 5223

Novel alpha 7-like nicotinic acetylcholine receptor subunits in the nematode Caenorhabditis elegans.

Mongan NP, Jones AK, Smith GR, Sansom MSP, Sattelle DB

Medline:

Citation:

Protein Science 11: 1162-1171 2002

Type:

ARTICLE

Genes:

acr-2 acr-3 acr-4 acr-5 acr-6 acr-7 acr-8 acr-9 acr-10 acr-11 acr-12 acr-13 acr-14 acr-15 acr-16 acr-17 acr-18 acr-19 acr-20 acr-21 acr-22 acr-23 deg-3 des-2 lev-1 unc-29 unc-38 unc-63

Abstract:

We have used reverse-transcription-polymerase chain reaction (RT-PCR) and DNA sequencing techniques to confirm the transcription of seven (six alpha and one non-alpha) novel candidate nicotinic acetylcholine receptor (nAChR) subunit-encoding genes identified in the genome sequence of the nematode Caenorhabditis elegans. Compared to vertebrate nAChR subunits. they most closely resemble the homomer-forming. neuronal alpha7 subunit. Comparison of the predicted amino acid sequences of the new nAChR subunits with those described previously in C. elegans reveals five subunits (four a and one non-alpha) which resemble the DEG-3-like group of subunits. To date. this highly divergent nAChR subunit group is unique to C. elegans. ACR-22 is the first non-a member of the DEG-3-like group of subunits to be identified. Two new members of the related ACR-16-like nAChR group of subunits have also been shown to be transcribed, making the ACR-16-like Subunit group the largest in C. elegans. Residues in the a subunit second transmembrane region (M2) which contribute to the channel lining show variations with implications for channel function. For example, in ACR-22, the highly conserved 0' lysine of M2 is replaced by histidine. Restrained molecular dynamics simulations have been used to generate molecular models of homo-pentameric M2 helix bundles for the novel subunits. enabling identification and display of pore-lining and protein inter-face residues. The number and diversity of genes encoding C. elegans nAChR subunits with similarities to the homomer-forming vertebrate alpha7 subunits and the identification of related non-a subunits. only found in C. elegans to date, suggest that at least some of these subunits may contribute to heteromers in