Rack1 Controls Parallel Fiber–Purkinje Cell Synaptogenesis and Synaptic Transmission

Rack1 Controls Parallel Fiber–Purkinje Cell Synaptogenesis and Synaptic Transmission
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Rack1 控制并行纤维 - 浦肯野细胞突触发生和突触传递

DOI:
10.3389/fncel.2019.00539
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发表时间:
2019-12
影响因子:
5.3
通讯作者:
Haitao Wu
Haitao Wu
中科院分区:
医学2区
文献类型:
--
作者:
Haihong Yang;Chaojuan Yang;Qian Zhu;Mengping Wei;Ying Li;Juanxian Cheng;Fengjiao Liu;Yan Wu;Jiyan Zhang;Chen Zhang;Haitao Wu

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小脑的浦肯野细胞(Purkinje cells,PC)接受颗粒细胞来源的平行纤维(parallel fiber,PF)和攀爬纤维两种兴奋性传入。支架蛋白Rack 1在小脑PC中高度表达。在这里,我们发现延迟形成特定的小脑蚓部小叶和受损的运动协调PC特异性Rack 1条件敲除小鼠。我们的研究进一步揭示了Rack 1在PF-PC突触形成中的重要作用。此外,Rack 1在调节PF-PC突触的突触可塑性和长时程抑制(LTD)诱导中起关键作用,而不改变突触后蛋白的表达。我们一起发现Rack 1是控制PF-PC突触发生和突触可塑性的关键分子。我们的研究为小脑神经发育和神经可塑性的机制提供了一个新的分子视角。
Purkinje cells (PCs) in the cerebellum receive two excitatory afferents including granule cells-derived parallel fiber (PF) and the climbing fiber. Scaffolding protein Rack1 is highly expressed in the cerebellar PCs. Here, we found delayed formation of specific cerebellar vermis lobule and impaired motor coordination in PC-specific Rack1 conditional knockout mice. Our studies further revealed that Rack1 is essential for PF–PC synapse formation. In addition, Rack1 plays a critical role in regulating synaptic plasticity and long-term depression (LTD) induction of PF–PC synapses without changing the expression of postsynaptic proteins. Together, we have discovered Rack1 as the crucial molecule that controls PF–PC synaptogenesis and synaptic plasticity. Our studies provide a novel molecular insight into the mechanisms underlying the neural development and neuroplasticity in the cerebellum.
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发表时间: 1999-05
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