| Autor: |
Xin-Tai Wang, Lin Zhou, Fang-Xiao Xu, De-Juan Wang, Xin-Yu Cai, Yin Wang, Sheng-Jian Ji, Martijn Schonewille, J. Julius Zhu, Chris I. De Zeeuw, Ying Shen |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.06.15.496308 |
| Popis: |
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. Presynaptic cAMP−EPAC−PKCε signaling cascade induces a previously unidentified threonine phosphorylation of RIM1α, and thereby initiates the assembly of the Rab3A−RIM1α−Munc13-1 tripartite complex that facilitates docking and release of synaptic vesicles. Granule cell-specific blocking of EPAC−PKCε 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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