The glutamate receptor subunit delta2 is capable of gating its intrinsic ion channel as revealed by ligand binding domain transplantation.
The family of ionotropic glutamate receptors includes 2 subunits, delta1 and delta2, the physiological relevance of which remains poorly understood. Both are nonfunctional in heterologous expression systems, although the isolated, crystallized ligand binding domain (LBD) of delta2 is capable of binding D-serine. To investigate these seemingly contradictory observations we tested whether delta receptors can be ligand gated at all. We used a strategy that replaced the native LBD of delta2 by a proven glutamate-binding LBD. Test transplantations between alpha-amino-3-hydroxy-5-methylisoxazole propionate (AMPA) and kainate receptors (GluR1 and GluR6, respectively) showed that this approach can produce functional chimeras even if only one part of the bipartite LBD is swapped. Upon outfitting delta2 with the LBD of GluR6, the chimera formed glutamate-gated ion channels with low Ca(2+) permeability and unique rectification properties. Ligand-induced conformational changes can thus gate delta2, suggesting that the LBD of this receptor works fundamentally differently from that of other ionotropic glutamate receptors.
Schmid
Sabine M
SM
Department of Biochemistry I-Receptor Biochemistry, International Graduate School of Neuroscience, Ruhr University Research School, Ruhr University Bochum, Bochum, Germany.
Kott
Sabine
S
Sager
Charlotte
C
Huelsken
Thomas
T
Hollmann
Michael
M
D000818:Animals; D015640:Ion Channel Gating; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D008024:Ligands; D017434:Protein Structure, Tertiary; D017470:Receptors, Glutamate / Q000235:genetics / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology; D014982:Xenopus laevis; D000097806:GluK2 Kainate Receptor
D007473:Ion Channels; D008024:Ligands; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D011993:Recombinant Fusion Proteins; D000097806:GluK2 Kainate Receptor; C107913:glutamate receptor delta 2