Rsph4a is essential for the triplet radial spoke head assembly of the mouse motile cilia


Autoři: Hiroshi Yoke aff001;  Hironori Ueno aff002;  Akihiro Narita aff003;  Takafumi Sakai aff001;  Kahoru Horiuchi aff001;  Chikako Shingyoji aff001;  Hiroshi Hamada aff004;  Kyosuke Shinohara aff001
Působiště autorů: Department of Biotechnology & Life Science, Tokyo University of Agriculture & Technology, Koganei, Tokyo, Japan aff001;  Molecular Function & Life Sciences, Aichi University of Education, Kariya, Aichi, Japan aff002;  Structural Biology Research Center, Graduate School of Science, Nagoya University, Nagoya, Aichi, Japan aff003;  Center for Biosystems Dynamics Research, RIKEN, Kobe, Japan aff004
Vyšlo v časopise: Rsph4a is essential for the triplet radial spoke head assembly of the mouse motile cilia. PLoS Genet 16(3): e32767. doi:10.1371/journal.pgen.1008664
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008664

Souhrn

Motile cilia/flagella are essential for swimming and generating extracellular fluid flow in eukaryotes. Motile cilia harbor a 9+2 arrangement consisting of nine doublet microtubules with dynein arms at the periphery and a pair of singlet microtubules at the center (central pair). In the central system, the radial spoke has a T-shaped architecture and regulates the motility and motion pattern of cilia. Recent cryoelectron tomography data reveal three types of radial spokes (RS1, RS2, and RS3) in the 96 nm axoneme repeat unit; however, the molecular composition of the third radial spoke, RS3 is unknown. In human pathology, it is well known mutation of the radial spoke head-related genes causes primary ciliary dyskinesia (PCD) including respiratory defect and infertility. Here, we describe the role of the primary ciliary dyskinesia protein Rsph4a in the mouse motile cilia. Cryoelectron tomography reveals that the mouse trachea cilia harbor three types of radial spoke as with the other vertebrates and that all triplet spoke heads are lacking in the trachea cilia of Rsph4a-deficient mice. Furthermore, observation of ciliary movement and immunofluorescence analysis indicates that Rsph4a contributes to the generation of the planar beating of motile cilia by building the distal architecture of radial spokes in the trachea, the ependymal tissues, and the oviduct. Although detailed mechanism of RSs assembly remains unknown, our results suggest Rsph4a is a generic component of radial spoke heads, and could explain the severe phenotype of human PCD patients with RSPH4A mutation.

Klíčová slova:

Cilia – Dyneins – Immunofluorescence – Microtubules – Sperm – Subcellular localization – Trachea – Tubulins


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