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Molecular structure of the chick cerebellar kainate-binding subunit of a putative glutamate receptor

Abstract

KAINATE receptors mediate some of the excitatory transactions carried out in the central nervous system by the neurotransmitter glutamate1. They are involved in neurotoxicity2, possibly in neurodegenerative disorders3 and it has been suggested that they have a role in long-term potentiation4. Kainate receptors are present both on neuronal1 and glial5–7 cell membranes where they regulate the gating of a voltage-independent ion channel8. Nothing is known about their molecular structure. Taking advantage of the unusually high abundance of 3H-kainate binding sites in the chick cerebellum9,10, 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 site11. The structure of this kainate binding protein (KBP) is also of interest because of its exclusive cerebellar localization on Bergmann glial membrane12 in close proximity to established glutamatergic synapses13. 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 channels14–16. 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.

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Gregor, P., Mano, I., Maoz, I. et al. Molecular structure of the chick cerebellar kainate-binding subunit of a putative glutamate receptor. Nature 342, 689–692 (1989). https://doi.org/10.1038/342689a0

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