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.
Villmann
C
C
Glutamate Receptor Laboratory, Max-Planck-Institute for Experimental Medicine, D-37075 Göttingen, Germany.
Bull
L
L
Hollmann
M
M
D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D002678:Chimera; D005260:Female; D006054:Goldfish; D007473:Ion Channels / Q000235:genetics*; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D011894:Rana pipiens; D017470:Receptors, Glutamate / Q000235:genetics; D018092:Kainic Acid Receptors / Q000235:genetics*; D014982:Xenopus laevis / Q000378:metabolism
D007473:Ion Channels; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors