Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor channels lacking the N-terminal domain.
Ionotropic glutamate receptor (iGluR) subunits contain a approximately 400-residue extracellular N-terminal domain ("X domain"), which is sequence-related to bacterial amino acid-binding proteins and to class C G-protein-coupled receptors. The X domain has been implicated in the assembly, transport to the cell surface, allosteric ligand binding, and desensitization in various members of the iGluR family, but its actual role in these events is poorly characterized. We have studied the properties of homomeric alpha-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA)-selective GluR-D glutamate receptors carrying N-terminal deletions. Our analysis indicates that, surprisingly, transport to the cell surface, ligand binding properties, agonist-triggered channel activation, rapid desensitization, and allosteric potentiation by cyclothiazide can occur normally in the complete absence of the X domain (residues 22-402). The relatively intact ligand-gated channel function of a homomeric AMPA receptor in the absence of the X domain indirectly suggests more subtle roles for this domain in AMPA receptors, e.g. in the assembly of heteromeric receptors and in synaptic protein interactions.
Pasternack
Arja
A
Institute of Biotechnology, Viikki Biocenter, P. O. Box 56, University of Helsinki, Viikinkaari 5, Helsinki FIN-00014, Finland.
Coleman
Sarah K
SK
Jouppila
Annukka
A
Mottershead
David G
DG
Lindfors
Maria
M
Pasternack
Michael
M
Keinänen
Kari
K
D000495:Allosteric Site; D000818:Animals; D001581:Benzothiadiazines / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D019281:Dimerization; D004232:Diuretics; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D017353:Gene Deletion; D006801:Humans; D020128:Inhibitory Concentration 50; D007313:Insecta; D007700:Kinetics; D008024:Ligands; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018091:Receptors, AMPA / Q000737:chemistry*; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology; D014162:Transfection
D001581:Benzothiadiazines; D004232:Diuretics; D008024:Ligands; D018091:Receptors, AMPA; D049993:Sodium Chloride Symporter Inhibitors; D004247:DNA; C004639:cyclothiazide