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题名

Camp−epac−pkcε−rim1α signaling regulates presynaptic long-term potentiation and motor learning

作者
通讯作者Zhu, J. Julius; De Zeeuw, Chris I.; Shen, Ying
共同第一作者Zhou, Lin; Dong, Bin-Bin; Xu,Fang-Xiao
发表日期
2023-04-26
DOI
发表期刊
ISSN
2050-084X
EISSN
2050-084X
卷号12页码:e80875
摘要

The cerebellum is involved in learning of fine motor skills, yet whether presynaptic plasticity contributes to such learning remains elusive. Here we report that the EPAC-PKCε module has a critical role in a presynaptic form of long-term potentiation in the cerebellum and motor behavior in mice. Presynaptic cAMP-EPAC-PKCε signaling cascade induces a previously unidentified threonine phosphorylation of RIM la, and thereby initiates the assembly of the Rab3A-RIMla-Muncl3-l tripartite complex that facilitates docking and release of synaptic vesicles. Granule cell-specific blocking of EPAC-PKCs signaling abolishes presynaptic long-term potentiation at the parallel fiber to Purkinje cell synapses and impairs basic performance and learning of cerebellar motor behavior. These results unveil a functional relevance of presynaptic plasticity that is regulated through a novel signaling cascade, thereby enriching the spectrum of cerebellar learning mechanisms.

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资助项目
National Innovation of Science and Technology-2030[81625006] ; National Natural Science Foundation of China["31820103005","32000692","32160192","32100791","31900741","32170976","2020YFB1313500"] ; National Key Research and Development Program of China[JCYJ20160331115633182] ; Science, Technology and Innovation Commission of Shenzhen Municipality[2019B030335001] ; Key Realm R&D Program of Guangdong Province[LQ17C090001] ; Ningxia Key Research and Development Program[20190101A10] ; Natural Science Foundation of Zhejiang Province[680235] ; null[2021ZD0204000] ; null[2021BEG03097]
WOS研究方向
Life Sciences & Biomedicine - Other Topics
WOS类目
Biology
WOS记录号
WOS:000986629000001
出版者
Scopus记录号
2-s2.0-85158911505
来源库
Scopus
引用统计
被引频次[WOS]:7
成果类型期刊论文
条目标识符http://sustech.caswiz.com/handle/2SGJ60CL/536620
专题生命科学学院_生物系
生命科学学院
作者单位
1.Department of Physiology and Department of Psychiatry,Sir Rim Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou,310058,China
2.Institute of Life Sciences,College of Life and Environmental Sciences,Hangzhou Normal University,Hangzhou,311121,China
3.Key Laboratory of Cranial Cerebral Diseases,Department of Neurobiology of Basic Medical College,Ningxia Medical University,Yinchuan,750004,China
4.Department of Biology,Southern University of Science and Technology,Shenzhen,518055,China
5.Department of Neuroscience,Erasmus MC,Rotterdam,3000 DR,Netherlands
6.Department of Pharmacology,University of Virginia,Charlottesville,22904,United States
7.Netherlands Institute for Neuroscience,Royal Academy of Sciences,Amsterdam,1105 BA,Netherlands
8.Intemational Institutes of Medicine,the Fourth Affiliated Hospital,Zhejiang University School of Medicine,Yiwu,China
9.Key Laboratory of Medical Neurobiology of Zhejiang Province,Zhejiang University School of Medicine,Hangzhou,China
推荐引用方式
GB/T 7714
Wang, Xin-Tai,Zhou, Lin,Dong, Bin-Bin,et al. Camp−epac−pkcε−rim1α signaling regulates presynaptic long-term potentiation and motor learning[J]. eLife,2023,12:e80875.
APA
Wang, Xin-Tai.,Zhou, Lin.,Dong, Bin-Bin.,Xu,Fang-Xiao.,Wang, De-Juan.,...&Shen, Ying.(2023).Camp−epac−pkcε−rim1α signaling regulates presynaptic long-term potentiation and motor learning.eLife,12,e80875.
MLA
Wang, Xin-Tai,et al."Camp−epac−pkcε−rim1α signaling regulates presynaptic long-term potentiation and motor learning".eLife 12(2023):e80875.
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