Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking

作者：Chowdhury Shoaib; Shepherd Jason D; Okuno Hiroyuki; Lyford Gregory; Petralia Ronald S; Plath Niels; Kuhl Dietmar; Huganir Richard L; Worley Paul F^*

来源：Neuron, 2006, 52(3): 445-459.

DOI：10.1016/j.neuron.2006.08.033

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.

• 出版日期2006-11-9