Elongation factor-2 phosphorylation in dendrites and the regulation of dendritic mRNA translation in neurons.
Elongation factor-2 phosphorylation in dendrites and the regulation of dendritic mRNA translation in neurons.
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DOI：
10.3389/fncel.2014.00035
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发表时间：
2014
影响因子：
5.3
通讯作者：
Sala C
中科院分区：
文献类型：
--
作者：
Heise C;Gardoni F;Culotta L;di Luca M;Verpelli C;Sala C
神经元活动通过调节树突中的 mRNA 翻译，导致突触结构和功能的长期持续变化。这些活动依赖性事件产生已知对突触修饰和不同形式的突触可塑性很重要的蛋白质的合成。值得注意的是，越来越多的证据表明真核延伸因子 2 激酶 (eEF2K)/真核延伸因子 2 (eEF2) 通路可能强烈参与这一过程。激活后，eEF2K 磷酸化，从而抑制 eEF2，导致 mRNA 翻译急剧减少。 eEF2K 由钙水平升高和钙调蛋白 (CaM) 结合激活，因此其替代名称为钙/CaM 依赖性蛋白激酶 III (CaMKIII)。在树突中，这一过程取决于谷氨酸信号传导和 N-甲基-D-天冬氨酸受体 (NMDAR) 激活。有趣的是，研究表明 eEF2K 也可以通过代谢型谷氨酸受体 (mGluR) 1/5 信号在树突中激活。因此，神经元活动可以通过改变 eEF2K 活性来诱导突触后局部蛋白质组变化。树突中 eEF2K 的既定靶标包括脑源性神经营养因子 (BDNF)、活性调节细胞骨架相关蛋白 (Arc)、钙/CaM 依赖性蛋白激酶 II (αCaMKII) 的 α 亚基和微管相关蛋白 1B (MAP1B)，所有这些都在不同形式的神经营养因子中具有众所周知的功能。 突触可塑性。在这篇综述中，我们将概述树突处的 eEF2K/eEF2 通路在 NMDAR 和神经元活性改变以及不同形式的突触可塑性（例如代谢型谷氨酸受体依赖性长期抑制（mGluR-LTD））背景下调节树突 mRNA 翻译的参与。为此，我们借鉴了体外和体内进行的研究。
Neuronal activity results in long lasting changes in synaptic structure and function by regulating mRNA translation in dendrites. These activity dependent events yield the synthesis of proteins known to be important for synaptic modifications and diverse forms of synaptic plasticity. Worthy of note, there is accumulating evidence that the eukaryotic Elongation Factor 2 Kinase (eEF2K)/eukaryotic Elongation Factor 2 (eEF2) pathway may be strongly involved in this process. Upon activation, eEF2K phosphorylates and thereby inhibits eEF2, resulting in a dramatic reduction of mRNA translation. eEF2K is activated by elevated levels of calcium and binding of Calmodulin (CaM), hence its alternative name calcium/CaM-dependent protein kinase III (CaMKIII). In dendrites, this process depends on glutamate signaling and N-methyl-D-aspartate receptor (NMDAR) activation. Interestingly, it has been shown that eEF2K can be activated in dendrites by metabotropic glutamate receptor (mGluR) 1/5 signaling, as well. Therefore, neuronal activity can induce local proteomic changes at the postsynapse by altering eEF2K activity. Well-established targets of eEF2K in dendrites include brain-derived neurotrophic factor (BDNF), activity-regulated cytoskeletal-associated protein (Arc), the alpha subunit of calcium/CaM-dependent protein kinase II (αCaMKII), and microtubule-associated protein 1B (MAP1B), all of which have well-known functions in different forms of synaptic plasticity. In this review we will give an overview of the involvement of the eEF2K/eEF2 pathway at dendrites in regulating the translation of dendritic mRNA in the context of altered NMDAR- and neuronal activity, and diverse forms of synaptic plasticity, such as metabotropic glutamate receptor-dependent-long-term depression (mGluR-LTD). For this, we draw on studies carried out both in vitro and in vivo.
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影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
影响因子：
34.7
作者：
Lisman, John;Yasuda, Ryohei;Raghavachari, Sridhar
通讯作者：
Raghavachari, Sridhar
影响因子：
3.7
作者：
Im HI;Nakajima A;Gong B;Xiong X;Mamiya T;Gershon ES;Zhuo M;Tang YP
通讯作者：
Tang YP
影响因子：
4.8
作者：
Lenz, G;Avruch, J
通讯作者：
Avruch, J
影响因子：
16.2
作者：
Kessels, Helmut W.;Malinow, Roberto
通讯作者：
Malinow, Roberto