Ligand-gated ion channel subunit partnerships: GABA(A) receptor α6 subunit gene inactivation inhibits δ subunit expression

A. Jones, E. R. Korpi, R. M. McKernan, R. Pelz, Z. Nusser, R. Mäkelä, J. R. Mellor, S. Pollard, S. Bahn, F. A. Stephenson, A. D. Randall, W. Sieghart, P. Somogyi, A. J.H. Smith, W. Wisden

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271 Citations (Scopus)

Abstract

Cerebellar granule cells express six GABA(A) receptor subunits abundantly (α1, α6, β2, β3, γ2, and δ) and assemble various pentameric receptor subtypes with unknown subunit compositions; however, the rules guiding receptor subunit assembly are unclear. Here, removal of intact α6 protein from cerebellar granule cells allowed perturbations in other subunit levels to be studied. Exon 8 of the mouse α6 subunit gene was disrupted by homologous recombination. In α6 -/- granule cells, the δ subunit was selectively degraded as seen by immunoprecipitation, immunocytochemistry, and immunoblot analysis with δ subunit-specific antibodies. The δ subunit mRNA was present at wild-type levels in the mutant granule cells, indicating a post-translational loss of the δ subunit. These results provide genetic evidence for a specific association between the α(B) and δ subunits. Because in α(B) -/- neurons the remaining α1, β(2/3), and γ2 subunits cannot rescue the δ subunit, certain potential subunit combinations may not be found in wild-type cells.

Original languageEnglish
Pages (from-to)1350-1362
Number of pages13
JournalJournal of Neuroscience
Volume17
Issue number4
Publication statusPublished - Feb 21 1997

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Keywords

  • GABA(A) receptor
  • Ro 15-4513
  • SR95531
  • cerebellum
  • dicistronic mRNA
  • flunitrazepam
  • gene targeting
  • granule cell
  • homologous recombination
  • internal ribosome entry site
  • knockout mice
  • ligand-gated ion channel
  • muscimol
  • subunit assembly
  • subunit sorting
  • transgenic mice
  • α subunit

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Jones, A., Korpi, E. R., McKernan, R. M., Pelz, R., Nusser, Z., Mäkelä, R., Mellor, J. R., Pollard, S., Bahn, S., Stephenson, F. A., Randall, A. D., Sieghart, W., Somogyi, P., Smith, A. J. H., & Wisden, W. (1997). Ligand-gated ion channel subunit partnerships: GABA(A) receptor α6 subunit gene inactivation inhibits δ subunit expression. Journal of Neuroscience, 17(4), 1350-1362.