• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Serum- and Glucocorticoid-Inducible Kinase 1 (SGK1) Increases Neurite Formation through Microtubule Depolymerization by SGK1 and by SGK1 Phosphorylation of tau
【24h】

Serum- and Glucocorticoid-Inducible Kinase 1 (SGK1) Increases Neurite Formation through Microtubule Depolymerization by SGK1 and by SGK1 Phosphorylation of tau

机译：血清和糖皮质激素诱导激酶1（SGK1）通过SGK1和SGK1的tau磷酸化通过微管解聚增加神经突形成。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Serum- and glucocorticoid-inducible kinase 1 (SGK1) is a member of the Ser/Thr protein kinase family that regulates a variety of cell functions. Recently, SGK1 was shown to increase dendritic growth but the mechanism underlying the increase is unknown. Here we demonstrated that SGK1 increased the neurite formation of cultured hippocampal neurons through microtubule (MT) depolymerization via two distinct mechanisms. First, SGK1 directly depolymerized MTs. In vitro MT depolymerization experiments revealed that SGK1, especially N-truncated SGK1, directly disassembled self-polymerized MTs and taxol-stabilized MTs in a dose-dependent and ATP-independent manner. The transfection of sgk1 to HeLa cells also inhibited MT assembly in vivo. Second, SGK1 indirectly depolymerized MTs through the phosphorylation of tau at Ser214. An in vitro kinase assay revealed that active SGK1 phosphorylated tau Ser214 specifically. In vivo transfection of sgk1 also phosphorylated tau Ser214 in HEK293T cells and hippocampal neurons. Further, sgk1 transfection significantly increased the number of primary neurites and shortened the length of the total process in cultured hippocampal neurons. These effects were antagonized by the cotransfection of the tauS214A mutant plasmid. Dexamethasone, a synthetic glucocorticoid, mimics the effect of sgk1 overexpression. Together, these results suggest that SGK1 enhances neurite formation through MT depolymerization by a direct action of SGK1 and by the SGK1 phosphorylation of tau.
机译：血清和糖皮质激素诱导激酶1（SGK1）是Ser / Thr蛋白激酶家族的成员，该家族调节多种细胞功能。最近，显示SGK1会增加树突状细胞的生长，但增加的潜在机制尚不清楚。在这里，我们证明了SGK1通过两种不同的机制通过微管（MT）解聚作用增加了培养的海马神经元的神经突形成。首先，SGK1直接解聚MT。体外MT解聚实验表明，SGK1，特别是N截短的SGK1，以剂量依赖性和ATP依赖性方式直接分解自聚合的MT和紫杉醇稳定的MT。 sgk1 转染HeLa细胞后，体内的MT组装也受到抑制。其次，SGK1通过Ser214处tau的磷酸化间接解聚了MT。体外激酶测定显示活性SGK1特异性磷酸化tau Ser214。 sgk1 的体内转染还在HEK293T细胞和海马神经元中磷酸化了tau Ser214。此外，在培养的海马神经元中， sgk1 转染显着增加了原代神经突的数量，并缩短了整个过程的长度。共转染 tau S214A突变质粒可拮抗这些作用。地塞米松是一种合成的糖皮质激素，模仿了 sgk1 过表达的作用。总之，这些结果表明，SGK1通过SGK1的直接作用和sau的SGK1磷酸化，通过MT解聚作用增强了神经突的形成。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号