Endophilin2 Interacts with GluA1 to Mediate AMPA Receptor Endocytosis Induced by Oligomeric Amyloid-β.
Endophilin2 Interacts with GluA1 to Mediate AMPA Receptor Endocytosis Induced by Oligomeric Amyloid-β.
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Endophilin2 与 GluA1 相互作用介导寡聚淀粉样蛋白-β 诱导的 AMPA 受体内吞作用
DOI：
10.1155/2017/8197085
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发表时间：
2017
影响因子：
3.1
通讯作者：
Guo G
中科院分区：
文献类型：
--
作者：
Zhang J;Yin Y;Ji Z;Cai Z;Zhao B;Li J;Tan M;Guo G
β淀粉样蛋白（Aβ）在阿尔茨海默病（AD）中起重要作用，因为寡聚Aβ诱导突触后AMPA受体（AMPAR）的丧失，导致认知缺陷。突触后AMPAR的丢失是通过网格蛋白依赖的内吞途径介导的，其中endophilin 2是重要的调节蛋白之一。在突触前膜和突触后膜中富集的Endophilin2先前已被报道对于突触前膜处的突触囊泡的再循环是重要的。然而，endophilin2在寡聚体Aβ诱导的突触后AMPAR内吞作用中的作用尚不清楚。在这项研究中，我们表明，endophilin2不影响组成AMPAR内吞作用。Endophilin2敲低，而不是过表达，抵抗寡聚Aβ诱导的AMPAR功能障碍。此外，endophilin 2与AMPAR亚基GluA 1共定位并相互作用，调节寡聚Aβ诱导的AMPAR内吞作用。因此，我们已经确定了endophilin2在寡聚体Aβ诱导的突触后AMPAR功能障碍中的作用，为预防认知障碍中AMPAR的丧失提供了可能的方向，并为AD的临床治疗提供了证据。
Amyloid-β (Aβ) plays an important role in Alzheimer's disease (AD), as oligomeric Aβ induces loss of postsynaptic AMPA receptors (AMPARs) leading to cognitive deficits. The loss of postsynaptic AMPARs is mediated through the clathrin-dependent endocytosis pathway, in which endophilin2 is one of the important regulatory proteins. Endophilin2, which is enriched in both the pre- and postsynaptic membrane, has previously been reported to be important for recycling of synaptic vesicles at the presynaptic membrane. However, the role of endophilin2 in oligomeric Aβ-induced postsynaptic AMPAR endocytosis is not well understood. In this study, we show that endophilin2 does not affect constitutive AMPAR endocytosis. Endophilin2 knockdown, but not overexpression, resisted oligomeric Aβ-induced AMPAR dysfunction. Moreover, endophilin2 colocalized and interacted with GluA1, a subunit of AMPAR, to regulate oligomeric Aβ-induced AMPAR endocytosis. Thus, we have determined a role of endophilin2 in oligomeric Aβ-induced postsynaptic AMPAR dysfunction, indicating possible directions for preventing the loss of AMPARs in cognitive impairment and providing evidence for the clinical treatment of AD.
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影响因子：
16.2
作者：
Milosevic I;Giovedi S;Lou X;Raimondi A;Collesi C;Shen H;Paradise S;O'Toole E;Ferguson S;Cremona O;De Camilli P
通讯作者：
De Camilli P
影响因子：
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影响因子：
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作者：
Cleary, JP;Walsh, DM;Ashe, KH
通讯作者：
Ashe, KH