Cilia locally synthesize proteins to sustain their ultrastructure and functions

Kai Hao,Xueliang Zhu,Xiumin Yan,Yawen Chen

doi:10.1038/s41467-021-27298-1

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.

Highlights

Cilia are microtubule-based hair-like organelles propelling locomotion and extracellular liquid flow or sensing environmental stimuli
To confirm that ribosomal proteins can be readily identified from motile cilia, we purified multicilia from cultured mouse ependymal cells (mEPCs) (Fig. 1a)[23], performed shotgun mass spectrometry[24], and hit 95% of known ribosomal components (Fig. 1b)
Our results suggest a mechanism in which Fmrp mediates the ciliary delivery of mRNAs through messenger ribonucleoprotein (mRNP) granules for ciliary local translation to facilitate the maintenance of ependymal multicilia (Fig. 8k)

Summary

Introduction

Cilia are microtubule-based hair-like organelles propelling locomotion and extracellular liquid flow or sensing environmental stimuli. It is recently recognized that mRNAs can be delivered to polarized subcellular compartments such as dendrites and axons in the form of messenger ribonucleoprotein (mRNP) granules to locally translate proteins. Such a mechanism enables the control of proteomes at spatiotemporal precision in response to regional or micro-environmental cues[2,3]. Ciliary proteins are generally believed to be synthesized primarily in the cytoplasm They translocate in the form of complexes or alone into the ciliary shaft, mainly through a trainlike motor-driven intraflagellar transport (IFT) machinery and rarely, usually for proteins less than 50 kDa, by diffusion[11,12,13]. Depriving the ciliary pool of Fmrp resulted in degeneration of ependymal multicilia

Methods

Results

Conclusion