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

Lorenzo A. Cingolani, Agnes Thalhammer, L. M Y Yu, Myriam Catalano, Timothy Ramos, Michael A. Colicos, Yukiko Goda

Research output: Contribution to journalArticle

Abstract

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 β3 integrins control synaptic strength by regulating AMPA receptors (AMPARs) in a subunit-specific manner. Pharmacological perturbation targeting β3 integrins promotes endocytosis of GluR2-containing AMPARs via Rap1 signaling, and expression of β3 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 β3 integrins, and in turn, β3 integrins are required for synaptic scaling. Our findings demonstrate a key role for integrins in the feedback regulation of excitatory synaptic strength.

Original languageEnglish
Pages (from-to)749-762
Number of pages14
JournalNeuron
Volume58
Issue number5
DOIs
Publication statusPublished - Jun 12 2008

Keywords

  • CELLBIO
  • MOLNEURO

ASJC Scopus subject areas

  • Neuroscience(all)

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    Cingolani, L. A., Thalhammer, A., Yu, L. M. Y., Catalano, M., Ramos, T., Colicos, M. A., & Goda, Y. (2008). Activity-Dependent Regulation of Synaptic AMPA Receptor Composition and Abundance by β3 Integrins. Neuron, 58(5), 749-762. https://doi.org/10.1016/j.neuron.2008.04.011