Proteasomal degradation of the metabotropic glutamate receptor 1α is mediated by Homer-3 via the proteasomal S8 ATPase: Signal transduction and synaptic transmission.
Proteasomal degradation of the metabotropic glutamate receptor 1α is mediated by Homer-3 via the proteasomal S8 ATPase: Signal transduction and synaptic transmission.
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DOI：
10.1111/j.1471-4159.2012.07752.x
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发表时间：
2012-07
影响因子：
4.7
通讯作者：
Mayer RJ
中科院分区：
文献类型：
--
作者：
Rezvani K;Baalman K;Teng Y;Mee MP;Dawson SP;Wang H;De Biasi M;Mayer RJ
代谢型谷氨酸受体（mGluRs）微调突触传递的功效。这种独特的功能使mGluRs成为治疗各种CNS疾病的潜在靶标。大量证据表明，泛素蛋白酶体系统介导突触强度的变化，导致多种形式的突触可塑性。本研究描述了突触后衔接子，长Homer-3蛋白和26 S蛋白酶体调节亚基之一，S8 ATP酶之间的一种新的相互作用，影响代谢型谷氨酸受体1α（mGluR 1 α）的降解。我们已经表明，这两个人长荷马-3蛋白特异性地与人蛋白酶体S8 ATP酶相互作用。我们在体外和体内均发现mGluR 1 α和长Homer-3s与26 S蛋白酶体发生免疫沉淀。我们进一步发现mGluR 1 α受体可以被26 S蛋白酶体泛素化和降解，Homer-3A促进了这一过程。此外，siRNA介导的Homer-3沉默导致总受体和质膜相关mGluR 1 α受体水平升高。这些结果表明，长Homer-3蛋白通过S8 ATP酶将泛素化的mGluR-1α受体穿梭到26 S蛋白酶体上来控制mGluR-1α受体的降解，这可能调节突触传递。
The metabotropic glutamate receptors (mGluRs) fine-tune the efficacy of synaptic transmission. This unique feature makes mGluRs potential targets for the treatment of various CNS disorders. There is ample evidence to show that the ubiquitin proteasome system mediates changes in synaptic strength leading to multiple forms of synaptic plasticity. The present study describes a novel interaction between post-synaptic adaptors, long Homer-3 proteins, and one of the 26S proteasome regulatory subunits, the S8 ATPase, that influences the degradation of the metabotropic glutamate receptor 1α (mGluR1α). We have shown that the two human long Homer-3 proteins specifically interact with human proteasomal S8 ATPase. We identified that mGluR1α and long Homer-3s immunoprecipitate with the 26S proteasome both in vitro and in vivo. We further found that the mGluR1α receptor can be ubiquitinated and degraded by the 26S proteasome and that Homer-3A facilitates this process. Furthermore, the siRNA mediated silencing of Homer-3 led to increased levels of total and plasma membrane-associated mGluR1α receptors. These results suggest that long Homer-3 proteins control the degradation of mGluR1α receptors by shuttling ubiquitinated mGluR-1α receptors to the 26S proteasome via the S8 ATPase which may modulate synaptic transmission.
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影响因子：
64.8
作者：
Ango, F;Prézeau, L;Fagni, L
通讯作者：
Fagni, L
影响因子：
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Finley D
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通讯作者：
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