Arc/Arg3.1 Interacts with the Endocytic Machinery to Regulate AMPA Receptor Trafficking

Shoaib Chowdhury, Jason D. Shepherd, Hiroyuki Okuno, Gregory Lyford, Ronald S. Petralia, Niels Plath, Dietmar Kuhl, Richard L. Huganir, Paul F. Worley

Research output: Contribution to journalArticle

Abstract

Arc/Arg3.1 is an immediate-early gene whose mRNA is rapidly transcribed and targeted to dendrites of neurons as they engage in information processing and storage. Moreover, Arc/Arg3.1 is known to be required for durable forms of synaptic plasticity and learning. Despite these intriguing links to plasticity, Arc/Arg3.1's molecular function remains enigmatic. Here, we demonstrate that Arc/Arg3.1 protein interacts with dynamin and specific isoforms of endophilin to enhance receptor endocytosis. Arc/Arg3.1 selectively modulates trafficking of AMPA-type glutamate receptors (AMPARs) in neurons by accelerating endocytosis and reducing surface expression. The Arc/Arg3.1-endocytosis pathway appears to regulate basal AMPAR levels since Arc/Arg3.1 KO neurons exhibit markedly reduced endocytosis and increased steady-state surface levels. These findings reveal a novel molecular pathway that is regulated by Arc/Arg3.1 and likely contributes to late-phase synaptic plasticity and memory consolidation.

Original languageEnglish (US)
Pages (from-to)445-459
Number of pages15
JournalNeuron
Volume52
Issue number3
DOIs
StatePublished - Nov 9 2006

Keywords

  • MOLNEURO
  • SIGNALING

ASJC Scopus subject areas

  • Neuroscience(all)

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    Chowdhury, S., Shepherd, J. D., Okuno, H., Lyford, G., Petralia, R. S., Plath, N., Kuhl, D., Huganir, R. L., & Worley, P. F. (2006). Arc/Arg3.1 Interacts with the Endocytic Machinery to Regulate AMPA Receptor Trafficking. Neuron, 52(3), 445-459. https://doi.org/10.1016/j.neuron.2006.08.033