The molecular dynamics of subdistal appendages in multi-ciliated cells

Hyunchul Ryu,Sejeong Hong,Soochul Park,Jiyeon Lee,Haeryung Lee,Hyuna Noh,Miram Shin,Vijay Kumar,Jaebong Kim

doi:10.1038/s41467-021-20902-4

Hyunchul Ryu, Sejeong Hong + Show 7 more

Open Access

https://doi.org/10.1038/s41467-021-20902-4

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Abstract

The motile cilia of ependymal cells coordinate their beats to facilitate a forceful and directed flow of cerebrospinal fluid (CSF). Each cilium originates from a basal body with a basal foot protruding from one side. A uniform alignment of these basal feet is crucial for the coordination of ciliary beating. The process by which the basal foot originates from subdistal appendages of the basal body, however, is unresolved. Here, we show FGFR1 Oncogene Partner (FOP) is a useful marker for delineating the transformation of a circular, unpolarized subdistal appendage into a polarized structure with a basal foot. Ankyrin repeat and SAM domain-containing protein 1A (ANKS1A) interacts with FOP to assemble region I of the basal foot. Importantly, disruption of ANKS1A reduces the size of region I. This produces an unstable basal foot, which disrupts rotational polarity and the coordinated beating of cilia in young adult mice. ANKS1A deficiency also leads to severe degeneration of the basal foot in aged mice and the detachment of cilia from their basal bodies. This role of ANKS1A in the polarization of the basal foot is evolutionarily conserved in vertebrates. Thus, ANKS1A regulates FOP to build and maintain the polarity of subdistal appendages.

Highlights

The motile cilia of ependymal cells coordinate their beats to facilitate a forceful and directed flow of cerebrospinal fluid (CSF)
By performing X-gal staining of lateral wall (LW) from Ankyrin repeat and sterile alpha motifs (SAMs) domain-containing protein 1A (ANKS1A)+/lacZ mice, we found strong ANKS1A expression during the first 10 days of postnatal (P) brain development that is gradually reduced after P20 (Fig. 1a) but never entirely lost
We found strong ANKS1A expression near multiple basal bodies (BBs) (Supplementary Fig. 1b) that was undetectable in the ependymal cells of ANKS1AlacZ/lacZ mice (referred to as ANKS1A knockout (KO) mice)

Summary

Introduction

The motile cilia of ependymal cells coordinate their beats to facilitate a forceful and directed flow of cerebrospinal fluid (CSF). Ciliary motility is critical for normal function in various tissues, including the circulation of cerebrospinal fluid (CSF) through brain ventricles, clearance of protective mucus from airways, and transport of eggs through oviducts[8,9,10,11,12,13] It remains unclear how MCCs orient with one another and coordinate ciliary beating at the molecular level. The orientation of the BF points in the direction of CSF flow, thereby conferring a onesided planar bias to the BB3,6,7 As it is with MCC in other tissues, the unidirectional alignment of all the basal feet on each E1 cell is referred to as the cell’s rotational polarity. While outer dense fiber 2 (ODF2), which is an essential scaffold for initiating the assembly of basal feet/SDAs, appears near the centriolar wall along the transverse axis of both

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