Conserved role for Ataxin-2 in mediating endoplasmic reticulum dynamics
Conserved role for Ataxin-2 in mediating endoplasmic reticulum dynamics
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DOI：
10.1111/tra.12647
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发表时间：
2019-06-01
期刊：
影响因子：
4.5
通讯作者：
Skop，Ahna R.
中科院分区：
文献类型：
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作者：
del Castillo，Urko;Gnazzo，Megan M.;Skop，Ahna R.
Aaxin-2是一种保守的RNA结合蛋白，与迟发性神经退行性疾病脊髓小脑型共济失调-2(SCA2)有关。SCA2的特点是小脑浦肯野神经元内的树突和鱼雷状轴突缩小。鱼雷样轴突被描述为含有移位的内质网(ER)在细胞的外围；然而，Aaxin-2在SCA2中介导ER功能的作用尚不清楚。我们利用Aaxin-2的线虫和果蝇同源物(分别为ATX-2和DATX2)来确定Aaxin-2在胚胎和神经元的内质网功能和动力学中的作用。ATX-2和DATX2的缺失导致胚胎细胞和生殖系分裂中的内质网崩溃，超微结构分析显示成熟卵母细胞中有独特的球状内质网堆叠，胚胎中的内质网小管碎裂和截断。ATX-2和DATX2位于两个C中与ER相邻的点点上。优雅的和果蝇的胚胎。最后，在培养的果蝇动脉瘤中DAtx2的缺失重现了SCA2缩小的树突状树枝的表型。这些神经元的内质网形态和动力学受到严重破坏。综上所述，我们提供了Aaxin-2在内质网动力学和形态公司中发挥进化保守作用的证据。雅典娜和果蝇胚胎在发育过程中和果蝇神经元中，提示可能的SCA2疾病机制。
Ataxin‐2, a conserved RNA‐binding protein, is implicated in the late‐onset neurodegenerative disease Spinocerebellar ataxia type‐2 (SCA2). SCA2 is characterized by shrunken dendritic arbors and torpedo‐like axons within the Purkinje neurons of the cerebellum. Torpedo‐like axons have been described to contain displaced endoplasmic reticulum (ER) in the periphery of the cell; however, the role of Ataxin‐2 in mediating ER function in SCA2 is unclear. We utilized theCaenorhabditis elegansandDrosophilahomologs of Ataxin‐2 (ATX‐2 and DAtx2, respectively) to determine the role of Ataxin‐2 in ER function and dynamics in embryos and neurons. Loss of ATX‐2 and DAtx2 resulted in collapse of the ER in dividing embryonic cells and germline, and ultrastructure analysis revealed unique spherical stacks of ER in mature oocytes and fragmented and truncated ER tubules in the embryo. ATX‐2 and DAtx2 reside in puncta adjacent to the ER in bothC. elegansandDrosophilaembryos. Lastly, depletion of DAtx2 in culturedDrosophilaneurons recapitulated the shrunken dendritic arbor phenotype of SCA2. ER morphology and dynamics were severely disrupted in these neurons. Taken together, we provide evidence that Ataxin‐2 plays an evolutionary conserved role in ER dynamics and morphology inC. elegansandDrosophilaembryos during development and in fly neurons, suggesting a possible SCA2 disease mechanism.