Human GluR6 kainate receptor (GRIK2): molecular cloning, expression, polymorphism, and chromosomal assignment.
Glutamate receptors mediate the majority of excitatory neurotransmission in the brain, and molecular cloning studies have revealed several distinct families. Because neuropathological states and possibly human disorders may involve kainate-preferring glutamate receptors, we have isolated a cDNA clone for the human GluR6 kainate-preferring receptor. This clone shows a very high sequence similarity with that of the rat, except for a part of the 3' untranslated region in which there is a TAA triplet repeat. When the protein was overexpressed in human embryonic kidney 293 cells, it had a molecular weight, an antibody recognition, and a glutamate ligand-binding profile similar to those of the rat GluR6 receptor. Northern analysis showed expression in both human cerebral and cerebellar cortices. By PCR analysis of rodent-human monochromosomal cell lines, the human GluR6 could be assigned to chromosome 6. The length of the TAA triplet repeat was polymorphic in the normal population, with at least four alleles and an observed heterozygosity of about 45%. These studies should provide the basis for expression or linkage studies of the GluR6 kainate receptor in human disease or neuropathologic states.
Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
W
W
Paschen
C D
CD
Blackstone
R L
RL
Huganir
C A
CA
Ross
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D003001:Cloning, Molecular / Q000379:methods; D015870:Gene Expression; D008040:Genetic Linkage; D015186:Hominidae / Q000235:genetics*; D006801:Humans; D007608:Kainic Acid / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D051381:Rats / Q000235:genetics; D018092:Kainic Acid Receptors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid
D007608:Kainic Acid; D018092:Kainic Acid Receptors