Journal article
The expression of dominant-negative subunits selectively suppresses neuronal AMPA and kainate receptors
Neuroscience, Vol.115(4), pp.1199-1210
2002
DOI: 10.1016/S0306-4522(02)00534-1
PMID: 12453491
Abstract
Glutamate-gated ion channels are widely expressed in neurons where they serve a host of cellular functions. An appealing, but yet unexplored, way to delineate the functions of particular glutamate receptor subtypes is to direct the expression of dominant-negative and gain-of-function mutant subunits. We tested the ability of two dominant-negative subunits, an α-amino-3-hydroxy-5-methyl-isoxazolproprionic acid receptor subunit and a kainate receptor subunit, to silence recombinant and neuronal glutamate receptors. Co-expression studies in non-neuronal cells indicated that the inclusion of a single mutant subunit was sufficient to silence the receptor. When expressed in cerebellar granule cells, the dominant-negative subunits silenced native channels in a subtype-specific fashion. Immunocytochemical staining of control and transfected neurons, as well as studies with a gain-of-function glutamate receptor-1 mutant, indicated that the mutant subunits were expressed at levels roughly equal to the total abundance of related native subunits, and both dominant-negatives suppressed native channel expression 60–65% when tested 24 h post-transfection. If co-assembly of the mutant subunits with related native subunits is combinatorial, this level of suppression gives receptor half-lives of approximately 20 h.
Details
- Title: Subtitle
- The expression of dominant-negative subunits selectively suppresses neuronal AMPA and kainate receptors
- Creators
- Antoine Robert - Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8066, USARhonda Hyde - Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8066, USAThomas E Hughes - Department of Ophthalmology and Visual Sciences, Yale University School of Medicine, 330 Cedar Street, New Haven, CT 06520-8066, USAJames R Howe - Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8066, USA
- Resource Type
- Journal article
- Publication Details
- Neuroscience, Vol.115(4), pp.1199-1210
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/S0306-4522(02)00534-1
- PMID
- 12453491
- ISSN
- 0306-4522
- eISSN
- 1873-7544
- Language
- English
- Date published
- 2002
- Academic Unit
- Surgery
- Record Identifier
- 9984051550302771
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