GLUTAMATE-RECEPTOR EDITING IN THE MAMMALIAN HIPPOCAMPUS AND AVIAN NEURONS

RNA editing determines receptor kinetics and permeability of glutamate receptors. This post-transcriptional modification alters single nucle otides within an RNA transcript changing the codon specified by the ge nome resulting in the incorporation of a different amino acid, profoun dly affecting the properties of the protein subunit. We have studied t he three sites subject to RNA editing within the kainate-specific subu nit GluR6 in the mammalian hippocampus to determine developmental chan ges and cell-specific variation in editing. GluR6, when measured in th e whole rat hippocampus, is predominantly expressed in the unedited fo rm at E18, with a gradual progression to the edited form during the 1s t post-natal week, and remains stable from P8 through 30 months. Indiv idual neurons from P0 through P8 rat hippocampal slices analyzed with single-cell PCR show predominant expression of fully edited GluR6, unl ike the population profile. In contrast, single astrocytes from P0 hip pocampal cultures show that the most common variant is partially edite d. Thus, editing in neurons and glia differs, and this difference acco unts for part of the disparity between single-neuron and whole-hippoca mpus data. Editing in astrocytes is affected by conditions in the exte rnal environment, as purified astrocytes fail to edit GluR6, although editing occurs in astrocytes from hippocampal cultures. The homogeneit y of GluR6 editing between species was also determined by comparing ed iting in avians and mammals. Genomic and cDNA analysis of chick glutam ate receptors demonstrates avian editing of GluR2 but not GluR6.