Alternative splicing of the GABA(A) receptor alpha 4 subunit creates a severely truncated mRNA.

Published

Journal Article

GABA(A) receptors, important sites of drug action, are chloride channels composed of 5 subunits chosen from among 19 or more. Alternative splicing for alpha 5, alpha 6, and rho 1 subunits results in truncated proteins which appear to lack function. We report a similar, relatively common (about 20%) form of alternative splicing of the alpha 4 subunit mRNA in mice and humans which, remarkably, creates a severely truncated message containing only the first two and last coding exons, with a frameshift in between. The only apparent translation product includes a short piece (39 amino acids) of the N-terminus right after the signal peptide. The splicing was developmentally and regionally regulated; the highest proportions of truncated alpha 4 mRNA, about 40%, were observed in embryonic day 18 whole brain and adult cerebellum. The truncated mRNA, when coexpresssed in human embryonic kidney (HEK) 293 cells with the complete alpha 4 subunit and beta1 and gamma 2 S subunits, reduced observed GABA currents without kinetic alterations. No such effect of truncated alpha 4 was observed with alpha1 subunit-containing receptors. Thus, the truncated alpha 4 N-terminus may play a post-translational regulatory role in intracellular folding/glycosylation/assembly of the alpha 4 subunit.

Full Text

Duke Authors

Cited Authors

  • Mu, W; Cheng, Q; Yang, J; Burt, DR

Published Date

  • September 15, 2002

Published In

Volume / Issue

  • 58 / 5

Start / End Page

  • 447 - 454

PubMed ID

  • 12242096

Pubmed Central ID

  • 12242096

International Standard Serial Number (ISSN)

  • 0361-9230

Digital Object Identifier (DOI)

  • 10.1016/s0361-9230(02)00816-x

Language

  • eng

Conference Location

  • United States