Journal
JOURNAL OF NEUROCHEMISTRY
Volume 94, Issue 2, Pages 531-546Publisher
WILEY
DOI: 10.1111/j.1471-4159.2005.03203.x
Keywords
biotinylation; exocytosis; glutamate receptor; integrin; long-term potentiation; trafficking
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Integrin proteins are critical for stabilization of hippocampal long-term potentiation but the mechanisms by which integrin activities are involved in synaptic transmission are not known. The present study tested whether activation of alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA) class glutamate receptors increases surface expression of alpha 5 beta 1 integrin implicated in synaptic potentiation. Surface protein biotinylation assays demonstrated that AMPA treatment of COS7 cells expressing GluR1 homomeric AMPA receptors increased membrane insertion and steady-state surface levels of alpha 5 and beta 1 subunits. Treated cells exhibited increased adhesion to fibronectin- and anti-alpha 5-coated substrates and tyrosine kinase signaling elicited by fibronectin-substrate adhesion, as expected if new surface receptors are functional. Increased surface expression did not occur in calcium-free medium and was blocked by the protein kinase C inhibitor chelerythrine chloride and the exocytosis inhibitor brefeldin A. AMPA treatment similarly increased alpha 5 and beta 1 surface expression in dissociated neurons and cultured hippocampal slices. In both neuronal preparations AMPA-induced integrin trafficking was blocked by combined antagonism of NMDA receptor and L-type voltage-sensitive calcium channel activities but was not induced by NMDA treatment alone. These results provide the first evidence that glutamate receptor activation increases integrin surface expression and function, and suggest a novel mechanism by which synaptic activity can engage a volley of new integrin signaling in coordination with, and probably involved in, stabilization of synaptic potentiation.
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