纖毛局部合成蛋白質(zhì)以維持其超微結(jié)構(gòu)和功能

2021年10月，中國(guó)科學(xué)院分子細(xì)胞科學(xué)**研究中心；上海生物化學(xué)與細(xì)胞生物學(xué)研究所；細(xì)胞生物學(xué)國(guó)家重點(diǎn)實(shí)驗(yàn)室；中國(guó)科學(xué)院大學(xué)；上海交通大學(xué)醫(yī)學(xué)院新華醫(yī)院早期生命健康研究所；兒童環(huán)境健康教育部上海市重點(diǎn)實(shí)驗(yàn)室；中國(guó)科學(xué)院大學(xué)杭州高等研究院生命科學(xué)學(xué)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老師研究團(tuán)隊(duì)在《Nature Communications》上發(fā)表論文：

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

“纖毛局部合成蛋白質(zhì)以維持其超微結(jié)構(gòu)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：

纖毛是基于微管的毛發(fā)狀細(xì)胞器，推動(dòng)運(yùn)動(dòng)和細(xì)胞外液體流動(dòng)或感知環(huán)境刺激。由于纖毛是阻斷擴(kuò)散的亞細(xì)胞區(qū)室，其蛋白質(zhì)成分被認(rèn)為是通過鞭毛內(nèi)運(yùn)輸或擴(kuò)散來自細(xì)胞體。在這里，我們發(fā)現(xiàn)纖毛局部合成蛋白質(zhì)以維持其結(jié)構(gòu)和功能。小鼠室管膜細(xì)胞多毛中含有豐富的核糖體蛋白、翻譯起始因子和RNA，包括18s rRNA和微管蛋白mRNA。纖毛活躍地產(chǎn)生新生多肽，包括微管蛋白。mRNA結(jié)合蛋白Fmrp定位于纖毛中央管腔，似乎在mRNA傳遞到纖毛中起作用。它被RNAi耗竭，損害纖毛局部翻譯，誘導(dǎo)多纖毛變性。外源性Fmrp的表達(dá)，而不是與線粒體相連的異構(gòu)體，挽救了變性缺陷。因此，纖毛的局部翻譯缺陷可能與纖毛病和其他疾病(如脆性X綜合征)的病理有關(guān)。

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