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

被引：597

作者：

Chowdhury, Shoaib

Shepherd, Jason D.

Okuno, Hiroyuki

Lyford, Gregory

Petralia, Ronald S.

Plath, Niels

Kuhl, Dietmar

Huganir, Richard L.

Worley, Paul F. ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Cellular & Mol Med Grad Program, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

[5] Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA

[6] Free Univ Berlin, Dept Biol Chem Pharm, D-14195 Berlin, Germany

来源：

NEURON | 2006年 / 52卷 / 03期

关键词：

D O I：

10.1016/j.neuron.2006.08.033

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：445 / 459

页数：15

共 78 条

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