当前位置: X-MOL 学术EMBO J. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
GSK3α, not GSK3β, drives hippocampal NMDAR‐dependent LTD via tau‐mediated spine anchoring
The EMBO Journal ( IF 9.4 ) Pub Date : 2020-11-16 , DOI: 10.15252/embj.2020105513
Jonathan E Draffin 1 , Carla Sánchez-Castillo 1 , Alba Fernández-Rodrigo 1 , Xavier Sánchez-Sáez 1 , Jesús Ávila 1 , Florence F Wagner 2 , José A Esteban 1
Affiliation  

Glycogen synthase kinase‐3 (GSK3) is an important signalling protein in the brain and modulates different forms of synaptic plasticity. Neuronal functions of GSK3 are typically attributed to one of its two isoforms, GSK3β, simply because of its prevalent expression in the brain. Consequently, the importance of isoform‐specific functions of GSK3 in synaptic plasticity has not been fully explored. We now directly address this question for NMDA receptor‐dependent long‐term depression (LTD) in the hippocampus. Here, we specifically target the GSK3 isoforms with shRNA knock‐down in mouse hippocampus and with novel isoform‐selective drugs to dissect their roles in LTD. Using electrophysiological and live imaging approaches, we find that GSK3α, but not GSK3β, is required for LTD. The specific engagement of GSK3α occurs via its transient anchoring in dendritic spines during LTD induction. We find that the major GSK3 substrate, the microtubule‐binding protein tau, is required for this spine anchoring of GSK3α and mediates GSK3α‐induced LTD. These results link GSK3α and tau in a common mechanism for synaptic depression and rule out a major role for GSK3β in this process.

中文翻译:


GSK3α(而非 GSK3β)通过 tau 介导的脊柱锚定驱动海马 NMDAR 依赖性 LTD



糖原合酶激酶 3 (GSK3) 是大脑中重要的信号蛋白,调节不同形式的突触可塑性。 GSK3 的神经元功能通常归因于其两种同工型之一 GSK3β,这仅仅是因为它在大脑中普遍表达。因此,GSK3 异构体特异性功能在突触可塑性中的重要性尚未得到充分探索。我们现在直接解决海马 NMDA 受体依赖性长期抑郁 (LTD) 的问题。在这里,我们专门针对小鼠海马中的 shRNA 敲低 GSK3 异构体,并使用新型异构体选择性药物来剖析它们在 LTD 中的作用。使用电生理学和实时成像方法,我们发现 LTD 需要 GSK3α,而不是 GSK3β。 GSK3α 的特异性参与是在 LTD 诱导过程中通过其短暂锚定在树突棘中而发生的。我们发现 GSK3α 的主要底物微管结合蛋白 tau 是 GSK3α 脊柱锚定所必需的,并介导 GSK3α 诱导的 LTD。这些结果将 GSK3α 和 tau 蛋白连接在突触抑制的共同机制中,并排除了 GSK3β 在此过程中的主要作用。
更新日期:2021-01-15
down
wechat
bug