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

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2006 Nov 8

PMID 17088211

Citations 421

Authors

Shoaib Chowdhury

Jason D Shepherd

Hiroyuki Okuno

Gregory Lyford

Ronald S Petralia

Niels Plath

Dietmar Kuhl

Richard L Huganir

Paul F Worley

Affiliations

Soon will be listed here.

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.

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