GENETIC REGULATION OF GLUTAMATE RECEPTOR ION CHANNELS

GENETIC REGULATION OF GLUTAMATE RECEPTOR ION CHANNELS ▪ Abstract Transcriptional and translational regulation of glutamate receptor expression determines one of the key phenotypic features of neurons in the brain—the properties of their excitatory synaptic receptors. Up- and down-regulation of various glutamate receptor subunits occur throughout development, following ischemia, seizures, repetitive activation of afferents, or chronic administration of a variety of drugs. The promoters of the genes that encode the NR1, NR2B, NR2C, GluR1, GluR2, and KA2 subunits share several characteristics that include multiple transcriptional start sites within a CpG island, lack of TATA and CAAT boxes, and neuronal-selective expression. In most cases, the promoter regions include overlapping Sp1 and GSG motifs near the major initiation sites, and a silencer element, to guide expression in neurons. Manipulating the levels of glutamate receptors in vivo by generating transgenic and knockout mice has enhanced understanding of the role of specific glutamate receptor subunits in long-term potentiation and depression, learning, seizures, neural pattern formation, and survival. Neuron-specific glutamate receptor promoter fragments may be employed in the design of novel gene-targeting constructs to deliver future experimental transgene and therapeutic agents to selected neurons in the brain. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annual Review of Pharmacology and Toxicology Annual Reviews

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Publisher
Annual Reviews
Copyright
Copyright © 1999 by Annual Reviews. All rights reserved
Subject
Review Articles
ISSN
0362-1642
eISSN
1545-4304
DOI
10.1146/annurev.pharmtox.39.1.221
pmid
10331083
Publisher site
See Article on Publisher Site

Abstract

▪ Abstract Transcriptional and translational regulation of glutamate receptor expression determines one of the key phenotypic features of neurons in the brain—the properties of their excitatory synaptic receptors. Up- and down-regulation of various glutamate receptor subunits occur throughout development, following ischemia, seizures, repetitive activation of afferents, or chronic administration of a variety of drugs. The promoters of the genes that encode the NR1, NR2B, NR2C, GluR1, GluR2, and KA2 subunits share several characteristics that include multiple transcriptional start sites within a CpG island, lack of TATA and CAAT boxes, and neuronal-selective expression. In most cases, the promoter regions include overlapping Sp1 and GSG motifs near the major initiation sites, and a silencer element, to guide expression in neurons. Manipulating the levels of glutamate receptors in vivo by generating transgenic and knockout mice has enhanced understanding of the role of specific glutamate receptor subunits in long-term potentiation and depression, learning, seizures, neural pattern formation, and survival. Neuron-specific glutamate receptor promoter fragments may be employed in the design of novel gene-targeting constructs to deliver future experimental transgene and therapeutic agents to selected neurons in the brain.

Journal

Annual Review of Pharmacology and ToxicologyAnnual Reviews

Published: Apr 1, 1999

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