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首页> 外文期刊>Neuron >Dynamic translational and proteasomal regulation of fragile X mental retardation protein controls mGluR-dependent long-term depression.
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Dynamic translational and proteasomal regulation of fragile X mental retardation protein controls mGluR-dependent long-term depression.

机译：动态翻译和蛋白酶体调节的脆弱X智力低下蛋白控制mGluR依赖的长期抑郁症。

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摘要

Genetic deletion of fragile X mental retardation protein (FMRP) has been shown to enhance mGluR-dependent long-term depression (LTD). Herein, we demonstrate that mGluR-LTD induces a transient, translation-dependent increase in FMRP that is rapidly degraded by the ubiquitin-proteasome pathway. Moreover, proteasome inhibitors abolished mGluR-LTD, and LTD was absent in mice that overexpress human FMRP. Neither translation nor proteasome inhibitors blocked the augmentation of mGluR-LTD in FMRP-deficient mice. In addition, mGluR-LTD is associated with rapid increases in the protein levels of FMRP target mRNAs in wild-type mice. Interestingly, the basal levels of these proteins were elevated and their synthesis was improperly regulated during mGluR-LTD in FMRP-deficient mice. Our findings indicate that hippocampal mGluR-LTD requires the rapid synthesis and degradation of FMRP and that mGluR-LTD triggers the synthesis of FMRP binding mRNAs. These findings indicate that the translation, ubiquitination, and proteolysis of FMRP functions as a dynamic regulatory system for controlling synaptic plasticity.
机译：脆性X智力低下蛋白（FMRP）的基因删除已显示出增强依赖mGluR的长期抑郁症（LTD）。在本文中，我们证明了mGluR-LTD引起FMRP的瞬时翻译依赖性增加，该增加被遍在蛋白-蛋白酶体途径迅速降解。此外，蛋白酶体抑制剂废除了mGluR-LTD，而过表达人FMRP的小鼠中没有LTD。翻译和蛋白酶体抑制剂都不能阻止FMRP缺陷小鼠中mGluR-LTD的扩增。另外，mGluR-LTD与野生型小鼠中FMRP靶mRNA的蛋白质水平快速增加有关。有趣的是，在FMRP缺陷小鼠的mGluR-LTD中，这些蛋白的基础水平升高，并且其合成受到不适当的调节。我们的发现表明，海马mGluR-LTD需要FMRP的快速合成和降解，而mGluR-LTD触发FMRP结合mRNA的合成。这些发现表明，FMRP的翻译，泛素化和蛋白水解是控制突触可塑性的动态调节系统。

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