The molecular dynamics of subdistal appendages in multi-ciliated cells

Hyunchul Ryu, Haeryung Lee, Jiyeon Lee, Hyuna Noh, Miram Shin, Vijay Kumar, Sejeong Hong, Jaebong Kim and Soochul Park ()
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Hyunchul Ryu: Sookmyung Women’s University
Haeryung Lee: Sookmyung Women’s University
Jiyeon Lee: Sookmyung Women’s University
Hyuna Noh: Sookmyung Women’s University
Miram Shin: Sookmyung Women’s University
Vijay Kumar: Hallym University
Sejeong Hong: Sookmyung Women’s University
Jaebong Kim: Hallym University
Soochul Park: Sookmyung Women’s University

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-20902-4

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