AMPA receptor stimulation increases α5β1 integrin surface expression, adhesive function and signaling

Abstract

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 α-amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA) class glutamate receptors increases surface expression of α5β1 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 α5 and β1 subunits. Treated cells exhibited increased adhesion to fibronectin- and anti-α5-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 α5 and β1 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. © 2005 International Society for Neurochemistry.