CDNA cloning of chick brain alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors reveals conservation of structure, function and post-transcriptional processes with mammalian receptors

Several types of functional ionotropic glutamate receptor have been cloned in the recent years from the mammalian central nervous system, but till now, none from other vertebrate species. Here, we report the cloning and functional analysis of four chick brain cDNAs, coding for members of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subtype of glutamate receptors. These receptors are highly homologous to the mammalian GluR1-4 (A-D) receptors (> 90%), and conserve their post-transcriptional modifications. The flip/flop exons are conserved not only at the amino acid level but also at the nucleotide level, and the intron of GluR4 involved in the RNA editing of the R/G site displays a rat-chick sequence conservation of 95%. Significant sequence differences are found only in the region containing the immunogenic epitope of neuroactive anti-GluR3 antibodies. Chick AMPA receptors are expressed in both the cerebrum and cerebellum The ion channel activities of chick GluR1-4 were analyzed in Xenopus oocytes and found to be similar to those of mammalian AMPA receptors. Though their contribution to kainate binding activity in the cerebellum is minor, the profile of channel activity of the chick GluR1-4 suggests that they account for the kainatergic channel activity expressed by total chick cerebellar mRNAs.