Investigation via ion pore transplantation of the putative relationship between glutamate receptors and K+ channels.
The pore domains of ionotropic glutamate receptors (iGluRs) and potassium channels (K(+) channels) show several structural similarities. To test for functional compatibility, we transferred pore regions from prokaryotic, invertebrate, and vertebrate K(+) channels into pharmacologically representative iGluRs and vice versa. Although the chimeric proteins were expressed on the cell surface, only one of 45 pore chimeras showed ion channel function: The kainate receptor subunit GluR6, carrying the pore loop plus adjacent transmembrane domains of the prokaryotic, glutamate-gated, K(+)-selective GluR0, adopted several electrophysiological properties of the donor pore upon pore transplantation. This suggests that, despite structural similarities between iGluR and K(+) channel pores, there is a lack of functional compatibility so that K(+) channel pores cannot be gated by the iGluR gating machinery, and vice versa. However, K(+)-selective pores can be gated in an iGluR sequence environment, given a similar signal transduction mechanism as appears to be present in GluR0.
Hoffmann
Jutta
J
Department of Biochemistry I-Receptor Biochemistry, Ruhr University Bochum, D-44780 Bochum, Germany.
Villmann
Carmen
C
Werner
Markus
M
Hollmann
Michael
M
D000818:Animals; D019921:Biotinylation / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002460:Cell Line; D003208:Concanavalin A / Q000493:pharmacokinetics; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D018698:Glutamic Acid / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D007608:Kainic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D016296:Mutagenesis / Q000502:physiology; D050506:Mutant Chimeric Proteins / Q000502:physiology; D009865:Oocytes; D018408:Patch-Clamp Techniques / Q000379:methods; D015221:Potassium Channels / Q000737:chemistry / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D017470:Receptors, Glutamate / Q000737:chemistry / Q000502:physiology*; D014162:Transfection; D014981:Xenopus
D050506:Mutant Chimeric Proteins; D015221:Potassium Channels; D017470:Receptors, Glutamate; D003208:Concanavalin A; D049452:Green Fluorescent Proteins; D018698:Glutamic Acid; D007608:Kainic Acid