The molecular dynamics of subdistal appendages in multi-ciliated cells

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.

The Tubulin Superfamily in Apicomplexan Parasites

“…In each case, the consequences of this loss are different. Drosophila centrioles lack subdistal appendages, structural elements that typically distinguish the mature (mother) centriole [ 21 , 85 , 86 , 87 ]. These nine triplet-containing structures are converted into basal bodies that template axonemes, including for motile flagella in sperm cells.…”

Goosecoid Controls Neuroectoderm Specification via Dual Circuits of Direct Repression and Indirect Stimulation in Xenopus Embryos

“…All MOs were obtained from Gene Tools (USA). For use, the MOs were diluted in sterile water and then heated at 65°C for 10 min before microinjections as described previously (Ryu et al, 2021). The harvested ACs were treated with activin (25 ng/ml) as described previously (Umair et al, 2020).…”

Microridge-like structures anchor motile cilia

“…Two types of rootlets, primarily composed of the ~225 kDa protein Rootletin, attach to the proximal end of MCC basal bodies, a prominent anterior rootlet located opposite to the basal foot, and a thinner rootlet projecting towards the cytoplasm 13 . The basal foot originates from subdistal appendages, requiring the presence of outer dense fiber 2 (ODF2), KIF3a, and Ankyrin repeat and SAM domain-containing protein 1A (ANKS1A) 25 – 27 . Rootlet and basal foot play important roles in resisting the mechanical forces imposed on the basal bodies of motile cilia 28 , 29 , but how basal bodies are precisely anchored to the apical plasma membrane remains unknown.…”