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Ligand-gated ion channel subunit partnerships: GABAA receptor alpha6 subunit gene inactivation inhibits delta subunit expression.

Authors
  • Jones, A1
  • 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
  • Wisden, W
  • 1 Medical Research Council Laboratory of Molecular Biology, Medical Research Council Centre, Cambridge CB2 2QH, United Kingdom. , (United Kingdom)
Type
Published Article
Journal
Journal of Neuroscience
Publisher
Society for Neuroscience
Publication Date
Feb 15, 1997
Volume
17
Issue
4
Pages
1350–1362
Identifiers
PMID: 9006978
Source
Medline
Language
English
License
Unknown

Abstract

Cerebellar granule cells express six GABAA receptor subunits abundantly (alpha1, alpha6, beta2, beta3, gamma2, and delta) and assemble various pentameric receptor subtypes with unknown subunit compositions; however, the rules guiding receptor subunit assembly are unclear. Here, removal of intact alpha6 protein from cerebellar granule cells allowed perturbations in other subunit levels to be studied. Exon 8 of the mouse alpha6 subunit gene was disrupted by homologous recombination. In alpha6 -/- granule cells, the delta subunit was selectively degraded as seen by immunoprecipitation, immunocytochemistry, and immunoblot analysis with delta subunit-specific antibodies. The delta subunit mRNA was present at wild-type levels in the mutant granule cells, indicating a post-translational loss of the delta subunit. These results provide genetic evidence for a specific association between the alpha6 and delta subunits. Because in alpha6 -/- neurons the remaining alpha1, beta2/3, and gamma2 subunits cannot rescue the delta subunit, certain potential subunit combinations may not be found in wild-type cells.

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