Kainate Binding Proteins Possess Functional Ion Channel Domains

Kainate binding proteins (KBPs) are highly homologous to ionotropic glutamate receptors; however, no ion channel function has been demonstrated for these proteins. To investigate possible reasons for the apparent lack of ion channel function we transplanted the ion channel domains of five KBPs into glutamate receptors GluR 6 and GluR1. In each case we obtained functional chimeric receptors in which glutamatergic agonists were able to open the KBP-derived ion channel with EC50 values identical to those of the subunit contributing the ligand binding domain. Maximal current amplitudes were significantly smaller than those of the parent clones, however. We also show that the KBP ion channels are highly permeable for calcium and have certain pharmacological properties that are distinct from all other glutamate receptor (GluR) subunits. Thus, all five known KBPs, in addition to their well characterized functional ligand binding sites, have functional ion permeation pathways. Our data suggest that the lack of ion channel function in wild-type KBPs results from a failure to translate ligand binding into channel opening. We interpret our findings to indicate the requirement for a modulatory protein or an additional subunit serving to alter the structure of the KBP subunit complex such that signal transduction is enabled from the ligand binding site to the intrinsically functional ion pore.

• Publication year

  1997

• Venue

  Journal of Neuroscience

• Publication date

  1997-10-15

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1523/JNEUROSCI.17-20-07634.1997PMID 9315885PMCID PMC6793921
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Wild-type kainate binding proteins appear to fail at coupling ligand binding to channel opening, implying that signal transduction from the ligand binding domain to the ion channel domain requires an additional modulatory factor.

  Confidence 0.90

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• Kainate binding protein ion channels were highly permeable to calcium and showed pharmacological properties distinct from other ionotropic glutamate receptor subunits.

  Confidence 0.96

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• Maximal current amplitudes in the chimeric receptors were significantly smaller than those of the parent clones.

  Confidence 0.93

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• Transplanting the ion channel domains of five kainate binding proteins into GluR6 or GluR1 produced functional chimeric receptors that could be opened by glutamatergic agonists.

  Confidence 0.98

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review

• calcium permeability

  ion transport property

  The extent to which a receptor channel conducts calcium ions relative to other ions.

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• chimeric receptors

  protein constructs

  Engineered receptor constructs made by swapping KBP ion channel domains into GluR6 or GluR1 backbones.

  Aliases: KBP-GluR chimeras

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• glutamatergic agonists

  ligands

  Glutamate-like activating molecules used to trigger the chimeric receptors in the assays described.

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• ion channel domain

  protein domains

  The receptor region responsible for ion conduction that was taken from KBP proteins in the chimera experiments.

  Aliases: pore-forming domain

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• ionotropic glutamate receptors

  protein family

  Ion channel receptors for glutamate used here as the scaffold and comparator family for the KBP chimeras.

  Aliases: iGluRs

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• kainate binding proteins

  protein family

  A family of glutamate receptor-related proteins examined for whether they contain functional ligand-binding and pore-forming regions.

  Aliases: KBPs

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• ligand binding domain

  protein domains

  The receptor region that binds ligand and was retained from the GluR subunit donor in the chimeric constructs.

  Aliases: LBD

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• ligand-binding donor subunit

  protein subunits

  The receptor subunit that supplied the ligand-binding domain for the chimeric receptor constructs.

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• parent clones

  controls

  The original receptor clones used as the non-chimeric comparison constructs for current amplitude measurements.

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• pharmacological properties

  properties

  The drug-response characteristics of the KBP-derived channels compared with other glutamate receptor subunits.

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review
• signal transduction

  molecular process

  The mechanism linking ligand binding to channel opening in the receptor complex.

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewq (76h6bfydm6) review

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