Linoleic Acid Derivative DCP-LA Stimulates Vesicular Transport of α7 ACh Receptors Towards Surface Membrane
Linoleic Acid Derivative DCP-LA Stimulates Vesicular Transport of α7 ACh Receptors Towards Surface Membrane
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DOI：
10.1159/000339049
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发表时间：
2012-01-01
影响因子：
--
通讯作者：
Nishizaki, Tomoyuki
中科院分区：
文献类型：
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作者：
Kanno, Takeshi;Tanaka, Akito;Nishizaki, Tomoyuki
背景/目的：我们之前发现亚油酸衍生物 DCP-LA 可以通过靶向 α7 ACh 受体来改善学习和记忆障碍。本研究旨在了解 DCP-LA 调节的 α7 ACh 受体运输。方法：我们监测非洲爪蟾卵母细胞中表达的 α7 ACh 受体的电流，并使用蔗糖密度梯度离心、突触体制备和来自大鼠海马切片的急性解离神经元的级分测定受体动员。结果：DCP-LA 持续增强 α7 ACh 受体电流，并且该作用被蛋白激酶 C (PKC) 抑制剂或囊泡转运抑制剂抑制。 DCP-LA 不会诱导 α7 ACh 受体的 PKC 磷酸化。 DCP-LA 刺激 α7 ACh 受体从胞质溶胶向质膜或从突触体外转移到突触体，并在海马神经元的突触前位点积累受体。结论：本研究的结果表明，DCP-LA 通过刺激受体的囊泡运输，增加海马神经元中 α 7 乙酰胆碱受体的表面定位，特别是在突触前末端，从而增强 α 7 乙酰胆碱受体反应，无论受体的 PKC 磷酸化如何。版权所有 (c) 2012 S. Karger AG，巴塞尔
Background/Aims: We have earlier found that the linoleic acid derivative DCP-LA could ameliorate learning and memory impairment by targeting alpha 7 ACh receptor. The present study aimed at understanding DCP-LA-regulated alpha 7 ACh receptor trafficking. Methods: We monitored currents through alpha 7 ACh receptors expressed in Xenopus oocytes and assayed the receptor mobilizations using fractions with a sucrose density gradient centrifugation, synaptosome preparation, and acutely dissociated neurons from rat hippocampal slices. Results: DCP-LA persistently potentiated alpha 7 ACh receptor currents, and the effect was inhibited by a protein kinase C (PKC) inhibitor or vesicular transport inhibitors. DCP-LA did not induce PKC phosphorylation of alpha 7 ACh receptors. DCP-LA stimulated translocation of alpha 7 ACh receptors from the cytosol toward the plasma membrane or from extra-synaptosomes into synaptosomes and accumulated the receptors at the presynaptic site in hippocampal neurons. Conclusion: The results of the present study demonstrate that DCP-LA increases surface localization of alpha 7 ACh receptors in hippocampal neurons, specifically at presynaptic terminals, by stimulating vesicular transport of the receptors, resulting in potentiation of alpha 7 ACh receptor responses, regardless of PKC phosphorylation of the receptors. Copyright (c) 2012 S. Karger AG, Basel