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- W4283015875 abstract "Abstract 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." @default.
- W4283015875 created "2022-06-18" @default.
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- W4283015875 date "2022-06-17" @default.
- W4283015875 modified "2023-09-30" @default.
- W4283015875 title "cAMP−EPAC−PKCε−RIM1α signaling regulates presynaptic long-term potentiation and motor learning" @default.
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- W4283015875 doi "https://doi.org/10.1101/2022.06.15.496308" @default.
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