Referenced in: none

Automatically associated channels: Kv2.1

Title: Small N-terminal deletion by splicing in cerebellar alpha 6 subunit abolishes GABAA receptor function.

Authors: E R Korpi, T Kuner, P Kristo, M Köhler, A Herb, H Lüddens, P H Seeburg

Journal, date & volume: J. Neurochem., 1994 Sep , 63, 1167-70

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/8051560

Abstract
Sequence variation was found in cDNA coding for the extracellular domain of the rat gamma-aminobutyric acid type A (GABAA) receptor alpha 6 subunit. About 20% of polymerase chain reaction (PCR)-amplified alpha 6 cDNA prepared from rat cerebellar mRNA lacked nucleotides 226-255 as estimated by counting single-stranded phage plaques hybridized specifically to the short (alpha 6S) and long (wild-type) forms of the alpha 6 mRNA. Genomic PCR revealed an intron located upstream of the 30-nucleotide sequence. Both splice forms were detected in the cerebellum by in situ hybridization. Recombinant receptors, resulting from coexpression of the alpha 6S subunit with the GABAA receptor beta 2 and gamma 2 subunits in human embryonic kidney 293 cells, were inactive at binding [3H]muscimol and [3H]Ro 15-4513. In agreement, injection of complementary RNAs encoding the same subunits into Xenopus oocytes produced only weak GABA-induced currents, indistinguishable from those produced by beta 2 gamma 2 receptors. Therefore, the 10 amino acids encoded by the 30-nucleotide fragment may be essential for the correct assembly or folding of the alpha 6 subunit-containing receptors.