Activity-Dependent Regulation of Synaptic AMPA Receptor Composition and Abundance by β3 Integrins

At synapses, cell adhesion molecules (CAMs) provide the molecular framework for coordinating signaling events across the synaptic cleft. Among synaptic CAMs, the integrins, receptors for extracellular matrix proteins and counterreceptors on adjacent cells, are implicated in synapse maturation and plasticity and memory formation. However, little is known about the molecular mechanisms of integrin action at central synapses. Here, we report that postsynaptic b3 integrins control synaptic strength by regulating AMPA receptors (AMPARs) in a subunit-specific manner. Pharmacological perturbation targeting b3 integrins promotes endocytosis of GluR2-containing AMPARs via Rap1 signaling, and expression of b3 integrins produces robust changes in the abundance and composition of synaptic AMPARs without affect- ingdendriticspinestructure. Importantly, homeostatic synaptic scaling induced by activity deprivation ele- vates surface expression of b3 integrins, and in turn, b3 integrins are required for synaptic scaling. Our findings demonstrate a key role for integrins in the feedback regulation of excitatory synaptic strength.