Spectrin-based membrane skeleton supports ciliogenesis
Spectrin-based membrane skeleton supports ciliogenesis
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基于血影蛋白的膜骨架支持纤毛发生
DOI：
10.1371/journal.pbio.3000369
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发表时间：
2019-07-01
期刊：
影响因子：
9.8
通讯作者：
Ou, Guangshuo
中科院分区：
文献类型：
--
作者：
Jia, Ru;Li, Dongdong;Ou, Guangshuo
纤毛是一种重要的细胞结构，它为细胞运动提供动力，传递细胞外信号。为了组装纤毛，一个由9个双线微管组成的圆柱形阵列推出质膜的延伸。膜张力调节纤毛的形成，然而，分子通路，机械刺激纤毛发生的联系尚不清楚。使用基因组编辑，我们将遗传性椭圆形红细胞增多症（HE）和脊髓小脑共济失调（SCA）相关突变引入秀丽隐杆线虫膜骨架蛋白血影蛋白。我们发现，这些突变损害质膜的机械支持和改变细胞形状。血影蛋白突变动物的RNA测序（RNA-seq）分析揭示了纤毛基因表达的全球下调，促使我们研究血影蛋白是否参与纤毛发生。血影蛋白突变影响鞭毛内转运（IFT），破坏轴丝微管，并抑制纤毛形成，和内源性血影蛋白周期性分布沿着纤毛。哺乳动物血影蛋白也定位于纤毛中并调节纤毛发生。这些结果定义了一个以前未被认识到的，但保守的作用，血影为基础的机械支持纤毛生物发生。
Cilia are remarkable cellular devices that power cell motility and transduce extracellular signals. To assemble a cilium, a cylindrical array of 9 doublet microtubules push out an extension of the plasma membrane. Membrane tension regulates cilium formation; however, molecular pathways that link mechanical stimuli to ciliogenesis are unclear. Using genome editing, we introduced hereditary elliptocytosis (HE)- and spinocerebellar ataxia (SCA)-associated mutations into the Caenorhabditis elegans membrane skeletal protein spectrin. We show that these mutations impair mechanical support for the plasma membrane and change cell shape. RNA sequencing (RNA-seq) analyses of spectrin-mutant animals uncovered a global down-regulation of ciliary gene expression, prompting us to investigate whether spectrin participates in ciliogenesis. Spectrin mutations affect intraflagellar transport (IFT), disrupt axonemal microtubules, and inhibit cilium formation, and the endogenous spectrin periodically distributes along cilia. Mammalian spectrin also localizes in cilia and regulates ciliogenesis. These results define a previously unrecognized yet conserved role of spectrin-based mechanical support for cilium biogenesis.