Inhibition by lectins of glutamate receptor desensitization is determined by the lectin's sugar specificity at kainate but not AMPA receptors.
The lectin Concanavalin A (ConA) has long been known to potentiate current responses of native and recombinant ionotropic glutamate receptors (iGluRs), apparently by inhibition of receptor desensitization. We compared the effects of a broad range of lectins with different carbohydrate specificities on recombinant AMPA (GluR1) and kainate receptors (GluR6) expressed in Xenopus oocytes. Interestingly, the extent of inhibition of desensitization appears to depend on the sugar preference of lectins at kainate (KA) receptors, but not at alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. None of the lectins potentiated current responses at non-glycosylated GluRs produced in tunicamycin-treated oocytes, demonstrating the requirement of lectin interaction with carbohydrate moieties of the receptors. At AMPA receptors, potentiation of current responses afforded by ConA and the well-known inhibitor of desensitization, cyclothiazide (CTZ), are additive, suggesting that the lectin and CTZ act independently. Current amplitudes of GluR1(L479Y), a nondesensitizing mutant, however, could not be further increased by ConA.
Thalhammer
Agnes
A
Department of Biochemistry I-Receptor Biochemistry, Ruhr University Bochum, NC6/170, D-44780 Bochum, Germany.
Everts
Inga
I
Hollmann
Michael
M
D000818:Animals; D001581:Benzothiadiazines / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D050260:Carbohydrate Metabolism; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D037102:Lectins / Q000378:metabolism / Q000494:pharmacology*; D037241:Mannose-Binding Lectins / Q000378:metabolism / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D009865:Oocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018091:Receptors, AMPA / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014817:Vitelline Membrane / Q000187:drug effects / Q000378:metabolism; D014981:Xenopus; D000097806:GluK2 Kainate Receptor
D001581:Benzothiadiazines; D037102:Lectins; D037241:Mannose-Binding Lectins; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor; C004639:cyclothiazide