Mannose-specific lectins modulate ligand binding to AMPA-type glutamate receptors.
Binding of [3H]AMPA was increased above control levels in rat brain membranes that had been incubated with concanavalin A (Con A) or a lectin from Lens culinaris (LC), both of which bind mannose residues. This did not occur with any of six lectins with other specificities. The magnitude of the increased binding varied from 15% in cortex to 70% in hippocampus and decreased significantly between 3 weeks and 6 months of age. Succinylated Con A was without effect and neither Con A nor LC increased binding to solubilized AMPA receptors. Increases in binding were not obtained in membranes purified from HEK293 cell lines expressing homomeric AMPA receptors. This indicates that mannose specific lectins may enhance binding by cross-linking AMPA receptors to each other or to proteins that are specific to brain. Con A has been reported to reduce glutamate receptor desensitization with higher efficacy at kainate than at AMPA receptors; the increase in binding reported here appears to be unrelated to such effects because (1) it was not affected by drugs that block desensitization and (2) [3H]kainate binding was reduced rather than increased by Con A. These observations suggest that AMPA receptor kinetic properties not involving desensitization are influenced by extracellular interactions between the receptors and other transmembrane proteins.
Hoffman
K B
KB
Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA 92697-3800, USA.
Kessler
M
M
Ta
J
J
Lam
L
L
Lynch
G
G
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D003208:Concanavalin A / Q000378:metabolism / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000737:chemistry; D015640:Ion Channel Gating / Q000187:drug effects*; D007700:Kinetics; D017774:Long-Term Potentiation / Q000502:physiology; D008358:Mannose / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000378:metabolism; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D003208:Concanavalin A; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D008358:Mannose; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid