title: Kainate-binding proteins are rendered functional ion channels upon transplantation of two short pore-flanking domains from a kainate receptor.
abstract: Kainate-binding proteins belong to an elusive class of putative ionotropic glutamate receptors that to date have not been shown to form functional ion channels in heterologous expression systems, despite binding glutamatergic agonists with high affinity. To test the hypothesis that inefficient or interrupted signal transduction from the ligand-binding site via linker domains to the ion pore (gating) might be responsible for this apparent lack of function, we transplanted the short homologous linker sequences from the fully functional rat kainate receptor GluR6 into frog kainate-binding protein. We were able to generate chimeric receptors that are functional in the Xenopus oocyte expression system and in human embryonic kidney 293 cells. The linker domains A and B in particular appear to be crucial for gating, because a functional kainate-binding protein was observed when at least parts of both linkers were derived from GluR6. We speculate that to enable signal transduction from the ligand-binding site to the ion pore of the frog kainate-binding protein, the linker structure of the protein has to undergo an essential conformational alteration, possibly mediated by an as yet unknown subunit or modulatory protein.
authors.affiliation: Department of Biochemistry I: Receptor Biochemistry, Ruhr University Bochum, Germany. naestrutz@hotmail.com
authors.forename: Nathalie
authors.initials: N
authors.lastname: Strutz
authors.forename: Carmen
authors.initials: C
authors.lastname: Villmann
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Breitinger
authors.forename: Markus
authors.initials: M
authors.lastname: Werner
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wenthold
authors.forename: Pablo
authors.initials: P
authors.lastname: Kizelsztein
authors.forename: Vivian I
authors.initials: VI
authors.lastname: Teichberg
authors.forename: Michael
authors.initials: M
authors.lastname: Hollmann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D051381:Rats; D018092:Kainic Acid Receptors / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014981:Xenopus
chemical_list: D007473:Ion Channels; D018092:Kainic Acid Receptors