Del Castillo Urko, Norkett Rosalind, Lu Wen, Serpinskaya Anna, Gelfand Vladimir I
Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
iScience. 2021 Dec 3;25(1):103536. doi: 10.1016/j.isci.2021.103536. eCollection 2022 Jan 21.
Ataxin-2 (Atx2) is a highly conserved RNA binding protein. Atx2 undergoes polyglutamine expansion leading to amyotrophic lateral sclerosis (ALS) or spinocerebellar ataxia type 2 (SCA2). However, the physiological functions of Atx2 in neurons remain unknown. Here, using the powerful genetics of we show that Atx2 is essential for normal neuronal cytoskeletal dynamics and organelle trafficking. Upon neuron-specific Atx2 loss, the microtubule and actin networks were abnormally stabilized and cargo transport was drastically inhibited. Depletion of Atx2 caused multiple morphological defects in the nervous system of third instar larvae. These include reduced brain size, impaired axon development, and decreased dendrite outgrowth. Defects in the nervous system caused loss of the ability to crawl and lethality at the pupal stage. Taken together, these data mark Atx2 as a major regulator of cytoskeletal dynamics and denote Atx2 as an essential gene in neurodevelopment, as well as a neurodegenerative factor.
ataxin-2（Atx2）是一种高度保守的RNA结合蛋白。Atx2发生多聚谷氨酰胺扩增会导致肌萎缩侧索硬化症（ALS）或2型脊髓小脑共济失调（SCA2）。然而，Atx2在神经元中的生理功能仍然未知。在这里，利用强大的遗传学方法，我们表明Atx2对于正常的神经元细胞骨架动力学和细胞器运输至关重要。在神经元特异性缺失Atx2后，微管和肌动蛋白网络异常稳定，货物运输受到严重抑制。Atx2的缺失在三龄幼虫的神经系统中导致了多种形态缺陷。这些缺陷包括脑尺寸减小、轴突发育受损和树突生长减少。神经系统的缺陷导致了爬行能力丧失和蛹期致死。综上所述，这些数据表明Atx2是细胞骨架动力学的主要调节因子，并表明Atx2是神经发育中的一个必需基因，也是一种神经退行性因子。
