Chihara Takahiro, Luginbuhl David, Luo Liqun
Howard Hughes Medical Institute, Department of Biological Sciences, 385 Serra Mall, Stanford University, Stanford, California 94305, USA.
Nat Neurosci. 2007 Jul;10(7):828-37. doi: 10.1038/nn1910. Epub 2007 May 27.
We identified a mutation in Aats-gly (also known as gars or glycyl-tRNA synthetase), the Drosophila melanogaster ortholog of the human GARS gene that is associated with Charcot-Marie-Tooth neuropathy type 2D (CMT2D), from a mosaic genetic screen. Loss of gars in Drosophila neurons preferentially affects the elaboration and stability of terminal arborization of axons and dendrites. The human and Drosophila genes each encode both a cytoplasmic and a mitochondrial isoform. Using additional mutants that selectively disrupt cytoplasmic or mitochondrial protein translation, we found that cytoplasmic protein translation is required for terminal arborization of both dendrites and axons during development. In contrast, disruption of mitochondrial protein translation preferentially affects the maintenance of dendritic arborization in adults. We also provide evidence that human GARS shows equivalent functions in Drosophila, and that CMT2D causal mutations show loss-of-function properties. Our study highlights different demands of protein translation for the development and maintenance of axons and dendrites.
我们通过一项镶嵌遗传筛选，在果蝇（黑腹果蝇）中鉴定出Aats - gly（也称为gars或甘氨酰 - tRNA合成酶）的一个突变，该基因是人类GARS基因的直系同源物，与2D型夏科 - 马里 - 图斯神经病（CMT2D）相关。果蝇神经元中gars的缺失优先影响轴突和树突终末分支的形成和稳定性。人类和果蝇基因各自编码一种细胞质异构体和一种线粒体异构体。利用选择性破坏细胞质或线粒体蛋白质翻译的其他突变体，我们发现细胞质蛋白质翻译是发育过程中树突和轴突终末分支形成所必需的。相比之下，线粒体蛋白质翻译的破坏优先影响成虫中树突分支的维持。我们还提供证据表明，人类GARS在果蝇中具有同等功能，并且CMT2D致病突变具有功能丧失特性。我们的研究突出了蛋白质翻译对轴突和树突发育及维持的不同需求。
