RSPH4A, the radial spoke head protein 4 homolog A, is involved in the assembly of radial spokes which are essential for motile cilia function. Radial spokes, with a T-shaped architecture in the central system of motile cilia, regulate ciliary motility and motion pattern [3]. Mutations in RSPH4A are associated with primary ciliary dyskinesia (PCD), a rare genetic ciliopathy [1].

In Rsph4a-deficient mice, cryoelectron tomography reveals that all triplet spoke heads are lacking in trachea cilia. Observation of ciliary movement and immunofluorescence analysis indicate that Rsph4a contributes to the generation of the planar beating of motile cilia by building the distal architecture of radial spokes in the trachea, ependymal tissues, and the oviduct [3]. In human PCD patients with RSPH4A mutations, it results in a clinical phenotype characterized by recurrent oto-sino-pulmonary infections [1]. Dysfunctional sperm flagellum and motile cilia in the respiratory tract and fallopian tube were found in patients with RSPH4A variants [2].

In conclusion, RSPH4A is crucial for the assembly of radial spoke heads in motile cilia, thus contributing to ciliary function. Studies on Rsph4a-deficient mouse models have revealed its role in ciliary motion and provided insights into the pathogenesis of PCD, which is characterized by respiratory defects, infertility, and other symptoms associated with abnormal ciliary function [1,2,3].

References:

1. De Jesús-Rojas, Wilfredo, Meléndez-Montañez, Jesús, Muñiz-Hernández, José, Ramos-Benitez, Marcos J, Mosquera, Ricardo A. 2023. The RSPH4A Gene in Primary Ciliary Dyskinesia. In International journal of molecular sciences, 24, . doi:10.3390/ijms24031936. https://pubmed.ncbi.nlm.nih.gov/36768259/

2. Wang, Lin, Wang, Rongchun, Yang, Danhui, Lei, Cheng, Luo, Hong. 2022. Novel RSPH4A Variants Associated With Primary Ciliary Dyskinesia-Related Infertility in Three Chinese Families. In Frontiers in genetics, 13, 922287. doi:10.3389/fgene.2022.922287. https://pubmed.ncbi.nlm.nih.gov/35812741/

3. Yoke, Hiroshi, Ueno, Hironori, Narita, Akihiro, Hamada, Hiroshi, Shinohara, Kyosuke. 2020. Rsph4a is essential for the triplet radial spoke head assembly of the mouse motile cilia. In PLoS genetics, 16, e1008664. doi:10.1371/journal.pgen.1008664. https://pubmed.ncbi.nlm.nih.gov/32203505/