Sialic acid residues indirectly modulate the binding properties of AMPA-type glutamate receptors.
Manipulations that disrupt the extracellular interactions of neural cell adhesion molecules (NCAMs) block the formation of stable long-term potentiation (LTP) but do not reverse already established potentiation. Several studies have implicated a change in AMPA-type glutamate receptors as being responsible for the expression of LTP but there are no evident links between NCAMs and the receptors. NCAMs are major carriers of sialic acid residues in the brain and removal of these with neuraminidase markedly affects the binding properties of the adhesion molecules. Therefore, the present study tested if neuraminidase treatment produces a change in AMPA receptors. Preincubation of cortical membranes with the enzyme for 15 min at 37 degrees C caused a approximately 5% reduction in the apparent sizes of NCAMs 140 and 180 but had no detectable influence on the sizes of various glutamate receptor subunits. The same treatment resulted in a 20 +/- 1% increase in the binding of [3H]AMPA with no apparent effect on binding to NMDA-type glutamate receptors or to high affinity kainate receptors. In membranes from the hippocampus, neuraminidase induced a 30 +/- 2% increase in binding which Scatchard analyses showed to be due to an increase in receptor affinity. Finally, neuraminidase had no effect on either the binding properties of solubilized AMPA receptors or on AMPA receptors stably expressed in a non-neuronal cell line. These results: (i) demonstrate that modulation of the extracellular environment can influence the binding properties of AMPA receptors, (ii) indicate that sialic acid residues in the extracellular compartment of synapses exert a significant and indirect influence on AMPA receptors and, (iii) suggest a route whereby NCAMs and LTP could be linked.
Hoffman
K B
KB
Center for the Neurobiology of Learning and Memory, University of California, Irvine 92697, USA.
Kessler
M
M
Lynch
G
G
D000818:Animals; D002460:Cell Line; D004350:Drug Residues / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D008566:Membranes / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000187:drug effects; D009439:Neuraminidase / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
D019006:Neural Cell Adhesion Molecules; D018091:Receptors, AMPA; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid