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首页> 外文期刊>Molecular and Cellular Biology >Neurexophilin 3 Is Highly Localized in Cortical and Cerebellar Regions and Is Functionally Important for Sensorimotor Gating and Motor Coordination
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Neurexophilin 3 Is Highly Localized in Cortical and Cerebellar Regions and Is Functionally Important for Sensorimotor Gating and Motor Coordination

机译：Neurexophilin 3高度局限在皮质和小脑区域，在功能上对感觉运动门控和运动协调很重要

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Neurexophilin 3 (Nxph3) is a specific ligand of synaptic α-neurexins that are essential for efficient neurotransmitter release. Previous biochemical work demonstrated that Nxph3 interacts with an extracellular domain of α-neurexins in a tight complex; however, no information is available on the localization or functional role of Nxph3 in the brain. Here, we generated lacZ reporter gene knock-in mice to investigate the distribution of Nxph3 at the single-cell level and Nxph3 knockout mice to examine its functional importance. Nxph3 expression was restricted mostly to subplate-derived neurons in cortical layer 6b, granule cells in the vestibulocerebellum, and Cajal-Retzius cells during development. Colabeling experiments demonstrated that neurons expressing Nxph3 do not belong to a uniform cell type. Morphological analyses and systematic behavioral testing of knockout mice revealed no anatomical defects but uncovered remarkable functional abnormalities in sensory information processing and motor coordination, evident by increased startle response, reduced prepulse inhibition, and poor rotarod performance. Since Nxph3-deficient mice behaved normally while performing a number of other tasks, our data suggest an important role for Nxph3 as a locally and temporally regulated neuropeptide-like molecule, presumably acting in a complex with α-neurexins in select neuronal circuits.
机译：Neurexophilin 3（Nxph3）是突触α-神经毒素的特定配体，对于有效的神经递质释放至关重要。先前的生化研究表明，Nxph3与紧密复合物中的α-神经毒素的胞外域相互作用。但是，尚无有关Nxph3在大脑中的定位或功能作用的信息。在这里，我们生成了 lacZ 报告基因敲入小鼠以研究Nxph3在单细胞水平上的分布，并产生了Nxph3敲除小鼠以检查其功能重要性。在发育过程中，Nxph3表达主要限于皮层6b中的亚板源性神经元，前庭小脑中的颗粒细胞和Cajal-Retzius细胞。共标记实验表明，表达Nxph3的神经元不属于统一的细胞类型。基因敲除小鼠的形态学分析和系统的行为测试没有发现解剖学上的缺陷，但是在感觉信息处理和运动协调中未发现明显的功能异常，这表现为惊吓反应增强，前冲抑制减少和旋转脚架性能差。由于缺乏Nxph3的小鼠在执行许多其他任务时行为正常，因此我们的数据表明Nxph3作为一种局部和时间调控的神经肽样分子具有重要作用，可能与选定的神经元回路中的α-神经毒素发生复合作用。

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