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

2006; Cell Press; Volume: 52; Issue: 3 Linguagem: Inglês

10.1016/j.neuron.2006.08.033

1097-4199

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

Cellular transport and secretion

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.