• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

蛋白激酶 A（PKA）对神经元功能的调节需要催化亚基与调节亚基的分离。

PKA regulation of neuronal function requires the dissociation of catalytic subunits from regulatory subunits.

机构信息

Vollum Institute, Oregon Health and Science University, Portland, United States.

出版信息

Elife. 2024 Nov 7;13:RP93766. doi: 10.7554/eLife.93766.

DOI:10.7554/eLife.93766
PMID:39508822
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11542917/
Abstract

Protein kinase A (PKA) plays essential roles in diverse cellular functions. However, the spatiotemporal dynamics of endogenous PKA upon activation remain debated. The classical model predicts that PKA catalytic subunits dissociate from regulatory subunits in the presence of cAMP, whereas a second model proposes that catalytic subunits remain associated with regulatory subunits following physiological activation. Here, we report that different PKA subtypes, as defined by the regulatory subunit, exhibit distinct subcellular localization at rest in CA1 neurons of cultured hippocampal slices. Nevertheless, when all tested PKA subtypes are activated by norepinephrine, presumably via the β-adrenergic receptor, catalytic subunits translocate to dendritic spines but regulatory subunits remain unmoved. These differential spatial dynamics between the subunits indicate that at least a significant fraction of PKA dissociates. Furthermore, PKA-dependent regulation of synaptic plasticity and transmission can be supported only by wildtype, dissociable PKA, but not by inseparable PKA. These results indicate that endogenous PKA regulatory and catalytic subunits dissociate to achieve PKA function in neurons.

摘要

蛋白激酶 A（PKA）在多种细胞功能中发挥着重要作用。然而，内源性 PKA 在被激活时的时空动力学仍然存在争议。经典模型预测，在 cAMP 的存在下，PKA 催化亚基与调节亚基解离，而第二个模型则提出，催化亚基在生理激活后仍与调节亚基结合。在这里，我们报告说，不同的 PKA 亚型，如由调节亚基定义的，在培养的海马切片 CA1 神经元中处于静止状态时表现出不同的亚细胞定位。然而，当所有被测试的 PKA 亚型都被去甲肾上腺素激活时，可能是通过β-肾上腺素能受体，催化亚基易位到树突棘，但调节亚基保持不动。这些亚基之间的差异空间动力学表明，至少有相当一部分 PKA 发生了解离。此外，只有可分离的 PKA 才能支持 PKA 依赖性的突触可塑性和传递的调节，而不可分离的 PKA 则不行。这些结果表明，内源性 PKA 的调节亚基和催化亚基发生解离，以实现在神经元中的 PKA 功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ec/11542917/be5e7be484c9/elife-93766-sa4-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ec/11542917/68ed00a4c2de/elife-93766-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ec/11542917/2f2ed9620f8c/elife-93766-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ec/11542917/65dd2246fd5f/elife-93766-fig1-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ec/11542917/31f3bc49f02b/elife-93766-fig1-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ec/11542917/037c638b9b17/elife-93766-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ec/11542917/d8e2cac9bd16/elife-93766-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ec/11542917/ad74fe3c6ec8/elife-93766-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ec/11542917/be5e7be484c9/elife-93766-sa4-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ec/11542917/68ed00a4c2de/elife-93766-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ec/11542917/2f2ed9620f8c/elife-93766-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ec/11542917/65dd2246fd5f/elife-93766-fig1-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ec/11542917/31f3bc49f02b/elife-93766-fig1-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ec/11542917/037c638b9b17/elife-93766-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ec/11542917/d8e2cac9bd16/elife-93766-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ec/11542917/ad74fe3c6ec8/elife-93766-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ec/11542917/be5e7be484c9/elife-93766-sa4-fig1.jpg

相似文献

1
PKA regulation of neuronal function requires the dissociation of catalytic subunits from regulatory subunits.蛋白激酶 A（PKA）对神经元功能的调节需要催化亚基与调节亚基的分离。
Elife. 2024 Nov 7;13:RP93766. doi: 10.7554/eLife.93766.
2
PKA regulation of neuronal function requires the dissociation of catalytic subunits from regulatory subunits.蛋白激酶A对神经元功能的调节需要催化亚基与调节亚基解离。
bioRxiv. 2024 Aug 20:2023.09.05.556437. doi: 10.1101/2023.09.05.556437.
3
Subcellular dynamics of type II PKA in neurons.神经元中II型蛋白激酶A的亚细胞动力学
Neuron. 2009 May 14;62(3):363-74. doi: 10.1016/j.neuron.2009.03.013.
4
Liberated PKA Catalytic Subunits Associate with the Membrane via Myristoylation to Preferentially Phosphorylate Membrane Substrates.游离的蛋白激酶A催化亚基通过肉豆蔻酰化与膜结合，优先磷酸化膜底物。
Cell Rep. 2017 Apr 18;19(3):617-629. doi: 10.1016/j.celrep.2017.03.070.
5
Regulation of neuronal PKA signaling through AKAP targeting dynamics.通过A激酶锚定蛋白靶向动力学对神经元蛋白激酶A信号传导的调节
Eur J Cell Biol. 2006 Jul;85(7):627-33. doi: 10.1016/j.ejcb.2006.01.010. Epub 2006 Feb 28.
6
Essential role for synaptopodin in dendritic spine plasticity of the developing hippocampus.突触足蛋白在发育海马树突棘可塑性中的重要作用。
J Neurosci. 2013 Jul 24;33(30):12510-8. doi: 10.1523/JNEUROSCI.2983-12.2013.
7
Regional differences in hippocampal PKA immunoreactivity after training and reversal training in a spatial Y-maze task.在空间Y迷宫任务中训练和逆向训练后海马体蛋白激酶A免疫反应性的区域差异。
Hippocampus. 2007;17(5):338-48. doi: 10.1002/hipo.20272.
8
Imaging ERK and PKA Activation in Single Dendritic Spines during Structural Plasticity.在结构可塑性过程中对单个树突棘中的细胞外信号调节激酶（ERK）和蛋白激酶A（PKA）激活进行成像
Neuron. 2017 Mar 22;93(6):1315-1324.e3. doi: 10.1016/j.neuron.2017.02.032. Epub 2017 Mar 9.
9
Synaptic plasticity through activation of GluA3-containing AMPA-receptors.通过激活含 GluA3 的 AMPA 受体实现突触可塑性。
Elife. 2017 Aug 1;6:e25462. doi: 10.7554/eLife.25462.
10
Estradiol rapidly modulates synaptic plasticity of hippocampal neurons: Involvement of kinase networks.雌二醇快速调节海马神经元的突触可塑性：激酶网络的参与。
Brain Res. 2015 Sep 24;1621:147-61. doi: 10.1016/j.brainres.2014.12.056. Epub 2015 Jan 13.

引用本文的文献

1
Transcranial iTBS Combined With Trans-Spinal iTBS Targeting PDE1A/cAMP/PKA Axis Regulates Neural Regeneration After Spinal Cord Injury.经颅间歇性θ波爆发刺激联合经脊髓间歇性θ波爆发刺激靶向PDE1A/cAMP/PKA轴调节脊髓损伤后的神经再生
CNS Neurosci Ther. 2025 Jul;31(7):e70525. doi: 10.1111/cns.70525.
2
The structures of protein kinase A in complex with CFTR: Mechanisms of phosphorylation and noncatalytic activation.蛋白激酶 A 与 CFTR 复合物的结构：磷酸化和非催化激活的机制。
Proc Natl Acad Sci U S A. 2024 Nov 12;121(46):e2409049121. doi: 10.1073/pnas.2409049121. Epub 2024 Nov 4.

本文引用的文献

1
Locomotion activates PKA through dopamine and adenosine in striatal neurons.运动通过纹状体神经元中的多巴胺和腺苷激活 PKA。
Nature. 2022 Nov;611(7937):762-768. doi: 10.1038/s41586-022-05407-4. Epub 2022 Nov 9.
2
AKAP79 enables calcineurin to directly suppress protein kinase A activity.AKAP79 使钙调磷酸酶能够直接抑制蛋白激酶 A 的活性。
Elife. 2021 Oct 6;10:e68164. doi: 10.7554/eLife.68164.
3
Myristoylation alone is sufficient for PKA catalytic subunits to associate with the plasma membrane to regulate neuronal functions.
仅仅豆蔻酰化就足以使 PKA 催化亚基与质膜结合，从而调节神经元功能。
Proc Natl Acad Sci U S A. 2021 Apr 13;118(15). doi: 10.1073/pnas.2021658118.
4
Swimming regulations for protein kinase A catalytic subunit.蛋白激酶 A 催化亚基的游泳规则。
Biochem Soc Trans. 2019 Oct 31;47(5):1355-1366. doi: 10.1042/BST20190230.
5
Mechanisms for restraining cAMP-dependent protein kinase revealed by subunit quantitation and cross-linking approaches.通过亚基定量和交联方法揭示抑制 cAMP 依赖性蛋白激酶的机制。
Proc Natl Acad Sci U S A. 2017 Sep 26;114(39):10414-10419. doi: 10.1073/pnas.1701782114. Epub 2017 Sep 11.
6
Local protein kinase A action proceeds through intact holoenzymes.局部蛋白激酶A的作用通过完整的全酶进行。
Science. 2017 Jun 23;356(6344):1288-1293. doi: 10.1126/science.aaj1669.
7
Liberated PKA Catalytic Subunits Associate with the Membrane via Myristoylation to Preferentially Phosphorylate Membrane Substrates.游离的蛋白激酶A催化亚基通过肉豆蔻酰化与膜结合，优先磷酸化膜底物。
Cell Rep. 2017 Apr 18;19(3):617-629. doi: 10.1016/j.celrep.2017.03.070.
8
Isoform-specific subcellular localization and function of protein kinase A identified by mosaic imaging of mouse brain.通过小鼠大脑的镶嵌成像鉴定蛋白激酶A的亚型特异性亚细胞定位和功能。
Elife. 2017 Jan 12;6:e17681. doi: 10.7554/eLife.17681.
9
An Isoform-Specific Myristylation Switch Targets Type II PKA Holoenzymes to Membranes.一种亚型特异性肉豆蔻酰化开关将II型蛋白激酶A全酶靶向至膜。
Structure. 2015 Sep 1;23(9):1563-1572. doi: 10.1016/j.str.2015.07.007. Epub 2015 Aug 13.
10
Intrinsic disorder within an AKAP-protein kinase A complex guides local substrate phosphorylation.A激酶附着蛋白-蛋白激酶A复合物中的内在无序性引导局部底物磷酸化。
Elife. 2013 Nov 5;2:e01319. doi: 10.7554/eLife.01319.