纤毛局部合成蛋白质以维持其超微结构和功能

2021年10月，中国科学院分子细胞科学**研究中心；上海生物化学与细胞生物学研究所；细胞生物学国家重点实验室；中国科学院大学；上海交通大学医学院新华医院早期生命健康研究所；儿童环境健康教育部上海市重点实验室；中国科学院大学杭州高等研究院生命科学学院(State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, 320 Yueyang Road, 200031 Shanghai, China；University of Chinese Academy of Sciences, 100049 Beijing, China；Ministry of Education Shanghai Key Laboratory of Children’s Environmental Health, Institute of Early Life Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine,200092 Shanghai,   China；School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 310024 Hangzhou, China) Xueliang Zhu老师研究团队在《Nature Communications》上发表论文：

“Cilia locally synthesize proteins to sustain their ultrastructure and functions”

“纤毛局部合成蛋白质以维持其超微结构和功能”

Abstract：

Cilia are microtubule-based hair-like organelles propelling locomotion and extracellular liquid flow or sensing environmental stimuli. As cilia are diffusion barrier-gated subcellular compartments, their protein components are thought to come from the cell body through intraflagellar transport or diffusion. Here we show that cilia locally synthesize proteins to maintain their structure and functions. Multicilia of mouse ependymal cells are abundant in ribosomal proteins, translation initiation factors, and RNA, including 18 S rRNA and tubulin mRNA. The cilia actively generate nascent peptides, including those of tubulin. mRNA-binding protein Fmrp localizes in ciliary central lumen and appears to function in mRNA delivery into the cilia. Its depletion by RNAi impairs ciliary local translation and induces multicilia degeneration. Expression of exogenous Fmrp, but not an isoform tethered to mitochondria, rescues the degeneration defects. Therefore, local translation defects in cilia might contribute to the pathology of ciliopathies and other diseases such as Fragile X syndrome.

摘要：

纤毛是基于微管的毛发状细胞器，推动运动和细胞外液体流动或感知环境刺激。由于纤毛是阻断扩散的亚细胞区室，其蛋白质成分被认为是通过鞭毛内运输或扩散来自细胞体。在这里，我们发现纤毛局部合成蛋白质以维持其结构和功能。小鼠室管膜细胞多毛中含有丰富的核糖体蛋白、翻译起始因子和RNA，包括18s rRNA和微管蛋白mRNA。纤毛活跃地产生新生多肽，包括微管蛋白。mRNA结合蛋白Fmrp定位于纤毛中央管腔，似乎在mRNA传递到纤毛中起作用。它被RNAi耗竭，损害纤毛局部翻译，诱导多纤毛变性。外源性Fmrp的表达，而不是与线粒体相连的异构体，挽救了变性缺陷。因此，纤毛的局部翻译缺陷可能与纤毛病和其他疾病(如脆性X综合征)的病理有关。

该论文中，HEK293T (ATCC, CRL-11268)和HEK293A细胞的体外培养是使用Ausbian特级胎牛血清完成的。欲了解或购买Ausbian特级胎牛血清可以联系北京缔一生物400-166-8600.