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J. Biol. Chem., Vol. 278, Issue 12, 10722-10730, March 21, 2003
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From the The present study provides the first evidence
that adhesion receptors belonging to the integrin family modulate
excitatory transmission in the adult rat brain. Infusion of an integrin
ligand (the peptide GRGDSP) into rat hippocampal slices reversibly
increased the slope and amplitude of excitatory postsynaptic
potentials. This effect was not accompanied by changes in paired pulse
facilitation, a test for perturbations to transmitter release, or
affected by suppression of inhibitory responses, suggesting by
exclusion that alterations to
Integrins Modulate Fast Excitatory Transmission at
Hippocampal Synapses*
§,
Department of Psychiatry and Human Behavior,
University of California, Irvine, California 92612-1695 and the
¶ Department of Anatomy and Neurobiology, University of
California, Irvine, California 92697-1275
-amino-3-hydroxy-5-methyl-4-isoxazole
propionate (AMPA)-type glutamate receptors cause the enhanced
responses. A mixture of function-blocking antibodies to integrin
subunits 3, 5, and
v blocked ligand effects on synaptic responses. The ligand-induced increases were (i) blocked by inhibitors of Src tyrosine
kinase, antagonists of N-methyl-D-aspartate
receptors, and inhibitors of calcium
calmodulin-dependent protein kinase II and (ii) accompanied
by phosphorylation of both the Thr286 site on
calmodulin-dependent protein kinase II and the
Ser831 site on the GluR1 subunit of the AMPA receptor.
N-Methyl-D-aspartate receptor antagonists
blocked the latter two phosphorylation events, but Src kinase
inhibitors did not. These results point to the conclusion that synaptic
integrins regulate glutamatergic transmission and suggest that they do
this by activating two signaling pathways directed at AMPA receptors.
*
This work was supported by NIMH, National Institutes of
Health (NIH), Grant MH61007 (to G. L.) and NINDS, NIH, Grant NS37799 (to C. M. G.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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