The Kinase Function of MSK1 Regulates BDNF Signaling to CREB and Basal Synaptic Transmission, But Is Not Required for Hippocampal Long-Term Potentiation or Spatial Memory.
The Kinase Function of MSK1 Regulates BDNF Signaling to CREB and Basal Synaptic Transmission, But Is Not Required for Hippocampal Long-Term Potentiation or Spatial Memory.
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DOI：
10.1523/eneuro.0212-16.2017
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发表时间：
2017-01
期刊：
影响因子：
3.4
通讯作者：
Frenguelli BG
中科院分区：
文献类型：
--
作者：
Daumas S;Hunter CJ;Mistry RB;Morè L;Privitera L;Cooper DD;Reyskens KM;Flynn HT;Morris RG;Arthur JS;Frenguelli BG
体外长时程增强（LTP）和体内空间记忆的后期阶段被认为取决于基因转录。因此，人们已经做了大量的尝试来确定转录调节的机制以及基因产物本身。以前的研究表明，一个转录调节因子，丝裂原和应激激活激酶1（MSK 1）的缺失，会导致空间记忆的损害。鉴于MSK 1通过cAMP反应元件结合蛋白（CREB）丝氨酸133（S133）磷酸化调节基因表达的能力，MSK 1是一个合理的候选者，作为一个主要的转录调节剂，支持突触可塑性和学习记忆。事实上，先前的工作已经揭示了MSK 1在稳态和经验依赖性突触可塑性中的必要性。然而，使用敲入激酶死亡的小鼠突变体的MSK 1，目前的研究表明，虽然激酶功能的MSK 1是重要的，在调节磷酸化CREB在S133和基础突触传递在海马CA 1区，它不是必需的代谢型谷氨酸受体依赖性长期抑郁症（mGluR-LTD），两种形式的LTP或几种形式的空间学习在水迷宫。这些数据表明，MSK 1的其他功能，如整个酶的结构作用，可以解释以前观察到的MSK 1在学习和记忆中的作用。
The later stages of long-term potentiation (LTP) in vitro and spatial memory in vivo are believed to depend upon gene transcription. Accordingly, considerable attempts have been made to identify both the mechanisms by which transcription is regulated and indeed the gene products themselves. Previous studies have shown that deletion of one regulator of transcription, the mitogen- and stress-activated kinase 1 (MSK1), causes an impairment of spatial memory. Given the ability of MSK1 to regulate gene expression via the phosphorylation of cAMP response element binding protein (CREB) at serine 133 (S133), MSK1 is a plausible candidate as a prime regulator of transcription underpinning synaptic plasticity and learning and memory. Indeed, prior work has revealed the necessity for MSK1 in homeostatic and experience-dependent synaptic plasticity. However, using a knock-in kinase-dead mouse mutant of MSK1, the current study demonstrates that, while the kinase function of MSK1 is important in regulating the phosphorylation of CREB at S133 and basal synaptic transmission in hippocampal area CA1, it is not required for metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD), two forms of LTP or several forms of spatial learning in the watermaze. These data indicate that other functions of MSK1, such as a structural role for the whole enzyme, may explain previous observations of a role for MSK1 in learning and memory.