Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking
Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking
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DOI：
10.1016/j.neuron.2006.08.033
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发表时间：
2006-11-09
期刊：
影响因子：
16.2
通讯作者：
Worley, Paul F.
中科院分区：
文献类型：
--
作者：
Chowdhury, Shoaib;Shepherd, Jason D.;Worley, Paul F.
Arc/Arg3.1是一种即时早期基因，其mRNA在神经元参与信息处理和存储时被快速转录并靶向神经元树突。此外，已知Arc/Arg3.1是突触可塑性和学习的持久形式所必需的。尽管有这些与可塑性的有趣联系，Arc/Arg3.1的分子功能仍然是谜。在这里，我们证明了Arc/Arg3.1蛋白与发动蛋白和特定的内亲和素亚型相互作用，以增强受体的内吞作用。Arc/Arg3.1通过加速内吞作用和减少表面表达选择性地调节神经元中AMPA型谷氨酸受体（AMPAR）的运输。Arc/Arg3.1-内吞途径似乎调节基础AMPAR水平，因为Arc/Arg3.1 KO神经元表现出明显减少的内吞作用和增加的稳态表面水平。这些发现揭示了一种新的分子通路，该通路由Arc/Arg3.1调节，并可能有助于晚期突触可塑性和记忆巩固。
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.