Accumulation of AMPA receptors in autophagosomes in neuronal axons lacking adaptor protein AP-4
Accumulation of AMPA receptors in autophagosomes in neuronal axons lacking adaptor protein AP-4
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DOI：
10.1016/j.neuron.2008.02.012
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发表时间：
2008-03-13
期刊：
影响因子：
16.2
通讯作者：
Yuzaki, Michisuke
中科院分区：
文献类型：
--
作者：
Matsuda, Shinji;Miura, Eriko;Yuzaki, Michisuke
AP-4是适配器蛋白复合体的一员，控制膜蛋白的囊泡运输。尽管AP-4被认为在上皮细胞的基侧分选中起作用，但它在神经元中的功能尚不清楚。在这里，我们发现编码AP-4 0亚基的基因的破坏导致了含有AMPA受体和跨膜AMPA受体调节蛋白(TARP)的轴突自噬小体在体外和体内的海马神经元和小脑浦肯野细胞的轴突中积累增加。AP-4通过TARPS与AMPA受体间接结合，AP-4与TARPS相互作用的特异性中断导致内源性AMPA受体在野生型神经元轴突中的错误定位。这些结果表明，AP-4可能调节其货物蛋白的适当的体树突特异性分布，包括AMPA受体-TARP复合体和神经元中的自噬途径。
AP-4 is a member of the adaptor protein complexes, which control vesicular trafficking of membrane proteins. Although AP-4 has been suggested to contribute to basolateral sorting in epithelial cells, its function in neurons is unknown. Here, we show that disruption of the gene encoding the 0 subunit of AP-4 resulted in increased accumulation of axonal autophagosomes, which contained AMPA receptors and transmembrane AMPA receptor regulatory proteins (TARPs), in axons of hippocampal neurons and cerebellar Purkinje cells both in vitro and in vivo. AP-4 indirectly associated with the AMPA receptor via TARPs, and the specific disruption of the interaction between AP-4 and TARPs caused the mislocalization of endogenous AMPA receptors in axons of wild-type neurons. These results indicate that AP-4 may regulate proper somatodendritic-specific distribution of its cargo proteins, including AMPA receptor-TARP complexes and the autophagic pathway in neurons.