Dynamics of local presynaptic protein synthesis of active zone components in spinal motoneurons

脊髓运动神经元活性区成分局部突触前蛋白合成的动力学

• 批准号: 405988308
• 负责人: Professor Dr. Markus Sauer
• 金额: --
• 依托单位: Institut für Klinische Neurobiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/405988308?language=en
• 关键词: Dynamics; local; presynaptic; protein; synthesis

Local protein synthesis in axon terminals plays a central role in axon guidance, postnatal differentiation of active zones and possibly also in synaptic plasticity of neuromuscular endplates. We have determined axonal transcriptomes in embryonic motoneurons and alterations of these transcriptomes in motoneurons from a mouse model of spinal muscular atrophy, the predominant form of motoneuron disease in children and young adults. Whereas the mRNAs for major active zone components such as Bassoon and Piccolo are mainly found in the somatodendritic compartments, the mRNA for Munc13-2 and Liprin-alpha-1 are highly enriched in axons and axonal terminals. Moreover, we found that the mRNAs encoding synaptophysin and VAMP2 are highly upregulated in the axonal compartment of Smn-deficient motoneurons. The goal of this project is to investigate the specific role of local translation of Munc13-2 in axon terminals of spinal motoneurons and to characterize the potential role of local Munc13-2 in disturbed synaptic function at neuromuscular endplates in spinal muscular atrophy. We expect new insights into the dynamics of local protein synthesis within active zones for physiological function of neuromuscular endplates and in motoneuron disease.

轴突终末的局部蛋白质合成在轴突导向、活动区的生后分化以及神经肌肉终板的突触可塑性中起着重要作用。我们已经确定了胚胎运动神经元的轴突转录组和这些转录组在运动神经元的脊髓性肌萎缩症，在儿童和年轻人的运动神经元疾病的主要形式的小鼠模型的改变。而主要的活性区成分，如巴松管和短笛的mRNA主要存在于体树突隔室，Munc 13 -2和Liprin-alpha-1的mRNA高度富集在轴突和轴突终末。此外，我们发现，编码突触体蛋白和VAMP 2的mRNA在Smn缺陷的运动神经元的轴突隔室中高度上调。本项目的目标是研究Munc 13 -2在脊髓运动神经元轴突终末中的局部翻译的具体作用，并描述局部Munc 13 -2在脊髓性肌萎缩症神经肌肉终板突触功能紊乱中的潜在作用。我们期待着新的见解，在神经肌肉终板的生理功能和运动神经元疾病的活动区内的局部蛋白质合成的动态。