Activity-dependent regulation of synaptic AMPA receptor composition and abundance by beta 3 integrins.
749 - 762.
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 beta 3 integrins control synaptic strength by regulating AMPA receptors (AMPARs) in a subunit-specific manner. Pharmacological perturbation targeting beta 3 integrins promotes endocytosis of GluR2-containing AMPARs via Rap1 signaling, and expression of beta 3 integrins produces robust changes in the abundance and composition of synaptic AMPARs without affecting dendritic spine structure. Importantly, homeostatic synaptic scaling induced by activity deprivation elevates surface expression of beta 3 integrins, and in turn, beta 3 integrins are required for synaptic scaling. Our findings demonstrate a key role for integrins in the feedback regulation of excitatory synaptic strength.
|Title:||Activity-dependent regulation of synaptic AMPA receptor composition and abundance by beta 3 integrins|
|Open access status:||An open access publication|
|Publisher version:||http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC24466...|
|Keywords:||LONG-TERM POTENTIATION, MOTOR-NERVE TERMINALS, HIPPOCAMPAL-NEURONS, GLUTAMATE RECEPTORS, TRANSMITTER RELEASE, ADHESION MOLECULES, NMDA RECEPTOR, SMALL GTPASES, PLASTICITY, TRANSMISSION|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Neuroscience, Physiology and Pharmacology|
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