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PMID: 9006978 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 17 ·No. 4 ·1997-02-15 ·Pages 1350-62

Jones A, Korpi ER, McKernan RM, Pelz R, Nusser Z, Mäkelä R, Mellor JR, Pollard S, Bahn S, Stephenson FA, Randall AD, Sieghart W, Somogyi P, Smith AJ, Wisden W

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.

MeSH Terms
Animals Behavior, Animal/physiology Benzodiazepines/pharmacology Cerebellum/cytology,drug effects,metabolism GABA Agonists/metabolism GABA Antagonists/metabolism GABA-A Receptor Antagonists Gene Expression Regulation Ion Channel Gating Ion Channels/metabolism Lac Operon Ligands Male Mice Mice, Knockout/genetics Muscimol/metabolism Neurons/metabolism Protein Processing, Post-Translational Pyridazines/metabolism RNA, Messenger/metabolism Receptors, GABA-A/genetics,metabolism
Chemicals
GABA Agonists GABA Antagonists GABA-A Receptor Antagonists Ion Channels Ligands Pyridazines RNA, Messenger Receptors, GABA-A Benzodiazepines Muscimol gabazine
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Jones A
Medical Research Council Laboratory of Molecular Biology, Medical Research Council Centre, Cambridge CB2 2QH, United Kingdom.
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
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
1997-02-15
Pages
1350-62
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6793744
Subset
IM
Databases
GENBANK
AJ222970
External Links
PubMed source PMC Full Text View journal details
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