α3, α5, and β4: Three members of the rat neuronal nicotinic acetylcholine receptor-related gene family form a gene cluster

J. Boulter, A. O'Shea-Greenfield, R. M. Duvoisin, J. G. Connolly, E. Wada, A. Jensen, P. D. Gardner, M. Ballivet, E. S. Deneris, D. McKinnon, S. Heinemann, J. Patrick

Research output: Contribution to journalArticlepeer-review

253 Scopus citations

Abstract

We have identified two additional members of the neuronal nicotinic acetylcholine receptor (nAChR)-related gene family. cDNA clones for one new gene, designated α5, were isolated from rat hippocampus and rat PC12 cell line cDNA libraries. The α5 gene encodes a protein of 48,800 daltons (424 amino acids) which exhibits significant overall amino acid sequence identity with the previously cloned rat nAChR subunits α1 (49%), α2 (55%), α3 (52%), and α4 (49%). Features characteristic of other nAChR α-subunits are present such as conserved cysteine residues at positions 127, 141, 191, and 192, and four strongly hydrophobic domains. A second addition to the nAChR-related gene family, designated β4, is encoded in overlapping rat genomic clones λDD15 and λRG518A. The β4 gene, encoding a mature protein of 53,300 daltons (475 amino acids), consists of 6 exons and has a transcription unit length of ~ 18 kilobase pairs. The β4 gene encoded protein shows considerable amino acid sequence identity with nAChR β1 (43%), β2 (64%), and β3 (44%) subunits. Northern blots showed that, along with α3 and β2, transcripts for both the α5 and β4 genes are present in the PC12 cell line, while in situ hybridization experiments demonstrated expression of the α5 and β4 genes in a small number of nuclei in the central nervous system. Finally, the genes that encode the β4, α3, and α5 proteins are transcribed with convergent polarities and form a tightly linked gene cluster spanning ~ 60 kilobase pairs.

Original languageEnglish (US)
Pages (from-to)4472-4482
Number of pages11
JournalJournal of Biological Chemistry
Volume265
Issue number8
StatePublished - 1990
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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