Molecular structure of the chick cerebellar kainate-binding subunit of a putative glutamate receptor.
Kainate receptors mediate some of the excitatory transactions carried out in the central nervous system by the neurotransmitter glutamate. They are involved in neurotoxicity, possibly in neurodegenerative disorders and it has been suggested that they have a role in long-term potentiation. Kainate receptors are present both on neuronal and glial cell membranes where they regulate the gating of a voltage-independent ion channel. Nothing is known about their molecular structure. Taking advantage of the unusually high abundance of 3H-kainate binding sites in the chick cerebellum, we have isolated an oligomeric protein that displays a pharmacological profile similar to that of a kainate receptor, and have demonstrated, using the monoclonal antibody IX-50, that this protein is composed of a single polypeptide of Mr 49,000 which harbours the specific kainate recognition site. The structure of this kainate binding protein (KBP) is also of interest because of its exclusive cerebellar localization on Bergmann glial membrane in close proximity to established glutamatergic synapses. We now report the isolation of the complementary DNA containing the complete coding region of the kainate binding protein. The predicted structure of the mature protein has four putative transmembrane domains with a topology analogous to that found in the superfamily of ligand-gated ion channels. This raises the possibility, that kainate binding protein may form part of an ion channel and may be a subunit of a kainate subtype of glutamate receptor.
Gregor
P
P
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Mano
I
I
Maoz
I
I
McKeown
M
M
Teichberg
V I
VI
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification*; D002531:Cerebellum / Q000032:analysis*; D002645:Chickens; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D007473:Ion Channels; D007608:Kainic Acid / Q000378:metabolism*; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter / Q000032:analysis* / Q000235:genetics / Q000302:isolation & purification*; D012689:Sequence Homology, Nucleic Acid
D002352:Carrier Proteins; D004247:DNA; D007473:Ion Channels; D007608:Kainic Acid; D046911:Macromolecular Substances; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter