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 a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. None of the lectins potentiated current responses at nonglycosylated 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.