Journal Article

Spectrin-based membrane skeleton supports ciliogenesis

Chai, Yongping, Huang, Xiaoshuai, Shao, Wenxin, Li, Ming, Li, Liuju, Li, Wei, Xie, Zhongyun, Li, Dongdong, Ou, Guangshuo, Chen, Liangyi, Xie, Chao, Liu, Yufan, Jia, Ru

2019

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Animals, Genetically Modified / Ataxia / Axonal transport / Biology / Biology and Life Sciences / Caenorhabditis elegans - embryology / Caenorhabditis elegans - genetics / Caenorhabditis elegans - metabolism / Caenorhabditis elegans Proteins - genetics / Caenorhabditis elegans Proteins - metabolism / Cell adhesion & migration / Cell Membrane - metabolism / Cell membranes / Cell size / Cilia / Cilia - genetics / Cilia - metabolism / Cilia - ultrastructure / Cilia and ciliary motion / Cytoskeletal proteins / Disease / Elliptocytosis / Evolution / Gene expression / Gene Expression Regulation, Developmental / Gene sequencing / Genes / Genetic aspects / Genome editing / Genomes / Kinases / Laboratories / Life sciences / Mechanical properties / Mechanical stimuli / Mechanics / Medicine / Membrane proteins / Membranes / Microscopy, Confocal / Microscopy, Electron, Transmission / Microtubules / Motility / Mutation / Nematodes / Physiological aspects / Proteins / Research and Analysis Methods / Ribonucleic acid / RNA / Sequence Analysis, RNA / Short Reports / Skeleton / Spectrin / Spectrin - genetics / Spectrin - metabolism