cAMP-EPAC-PKCε-RIM1α signaling regulates presynaptic long-term potentiation and motor learning.
cAMP-EPAC-PKCε-RIM1α signaling regulates presynaptic long-term potentiation and motor learning.
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作者：
Wang XT;Zhou L;Dong BB;Xu FX;Wang DJ;Shen EW;Cai XY;Wang Y;Wang N;Ji SJ;Chen W;Schonewille M;Zhu JJ;De Zeeuw CI;Shen Y
小脑参与精细运动技能的学习，然而突触前可塑性是否有助于这种学习仍然是难以捉摸的。在这里，我们报告EPAC-PKCε模块在小鼠小脑和运动行为的突触前形式的长时程增强中具有关键作用。突触前cAMP−EPAC−PKCε信号级联诱导先前未鉴定的RIM 1 α的苏氨酸磷酸化，从而启动Rab 3A − RIM 1 α− Munc 13 -1三联复合物的组装，促进突触囊泡的对接和释放。颗粒细胞特异性阻断EPAC−PKCε信号传导可消除平行纤维至浦肯野细胞突触的突触前长时程增强，并损害小脑运动行为的基本表现和学习。这些结果揭示了突触前可塑性的功能相关性，通过一种新的信号级联调节，从而丰富了小脑学习机制的频谱。
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 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.
影响因子：
5.8
作者：
Roscioni SS;Kistemaker LE;Menzen MH;Elzinga CR;Gosens R;Halayko AJ;Meurs H;Schmidt M
通讯作者：
Schmidt M