Identifications, Classification, and Evolution of the Vertebrate α-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionic Acid (AMPA) Receptor Subunit Genes

Abstract

The AMPA receptor (AMPAR), a pharmacologically defined ionotropic glutamate receptor, mediates fast excitatory synaptic transmission in the vertebrate central nervous system. Mammalian and avian AMPARs are assembled from the products of four genes (GRIA1-GRIA4) conserved in their translated sequences and gene organizations. Teleost fish also express AMPAR subunits; however, the AMPAR genes have not been extensively investigated in lower vertebrates. To elucidate the evolution of vertebrate AMPAR genes, reverse-transcriptase PCR-based surveys of subunits expressed in the brains of eight nonmammalian vertebrates were performed. The newly cloned vertebrate AMPAR subunits were classified by their sequence identities to the mammalian AMPAR subunits. The results of molecular and phylogenetic analyses indicated that the members of the AMPAR gene family increased from two in the jawless hagfish to four in the tetrapods and the shark and to more than four in the teleost fish. The sizes of AMPAR gene families correlate well with those of many multigene families observed in various vertebrates. Moreover, all vertebrates expressed at least one AMPAR subunit bearing an arginine (R) at the Q/R site, at which no invertebrate glutamate receptor subunit has been found to have an R residue, suggesting that the low calcium-permeable AMPARs appeared at early evolutionary stages of vertebrate central nervous systems. Uniquely, the loop 1 (L1) regions between hydrophobic domain 1 and hydrophobic domain 2 of the hagfish putative GRIA2 and all the teleost GRIA1 subunits were much longer than those of the remaining known ionotropic glutamate receptor subunits. The length and sequence of the L1 of teleost GRIA1 subunits were heterogeneous, suggesting that the amino acid residues in L1 were not highly selected.

Genome-wide scan of bipolar disorder in 65 pedigrees: supportive evidence for linkage at 8q24, 18q22, 4q32, 2p12, and 13q12

“…Potential candidate genes for consideration include: the tryptophan oxygenase gene (TDO2) 45 and potentially genes encoding a glycine receptor (GLRB) 46 and glutamate receptor (GRIA2). 47 We observed a second peak on chromosome 4 at marker D4S3051 on 4q35 (NPL ¼ 2.43, Po0.01). This region overlaps with a report by Adams et al 48 who found a parametric LOD ¼ 3.19 under a dominant model and broad affection status.…”

AMPA glutamate receptors are required for sensory-organ formation and morphogenesis in the basal chordate

“…Thus, Ciona has only Ca-P GluAs throughout its life span because ciGluAs are the sole AMPA-type receptor in this species. Other invertebrates, such as nematodes and flies, have also been reported to have only Q-type GluAs (50). The requirement for Ca-I GluAs in mammals appears to be evolutionarily unique and may be related to the role of GluAs in synaptic transmission acquired during the evolution of vertebrates.…”

Retinotectal transmission in the optic tectum of rainbow trout

“…6A, right). This additional band might be a homologue of GluR2, because the teleost brain contains multiple homologues of a single gene of mammalian AMPA receptor (Chen et al, 2001). Alternatively, the additional band might represent a different glycosylation form or a splicing form.…”