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Abstract
Calaxin is a Ca2+-binding dynein-associated protein that regulates flagellar and ciliary movement. In ascidians, calaxin plays essential roles in chemotaxis of sperm. However, nothing has been known for the function of calaxin in vertebrates. Here we show that the mice with a null mutation in Efcab1, which encodes calaxin, display typical phenotypes of primary ciliary dyskinesia, including hydrocephalus, situs inversus, and abnormal motility of trachea cilia and sperm flagella. Strikingly, both males and females are viable and fertile, indicating that calaxin is not essential for fertilization in mice. The 9 + 2 axonemal structures of epithelial multicilia and sperm flagella are normal, but the formation of 9 + 0 nodal cilia is significantly disrupted. Knockout of calaxin in zebrafish also causes situs inversus due to the irregular ciliary beating of Kupffer’s vesicle cilia, although the 9 + 2 axonemal structure appears to remain normal.
Highlights
Genetic defects of the dynein components cause primary ciliary dyskinesia (PCD), a human ciliopathy disease[6,7,8]
In Ciona, calaxin is essential for chemotaxis of the sperm to the egg; both male and female Efcab1−/− mice were fertile, litter sizes when either or both parents were Efcab1−/− were significantly lower compared with litters from wild-type parents (Fig. 1g)
Hydrocephalus emerges after birth and is not always lethal[33]; the cause of embryonic lethality is most likely to result from cardiac defects that often accompany PCD34
Summary
Genetic defects of the dynein components cause primary ciliary dyskinesia (PCD), a human ciliopathy disease[6,7,8]. PCD is most often caused by defects in a subunit of the ODA, including HCs (DNAH5 and DNAH11), ICs (DNAI1, DNAI2 and TXNDC3/NME8), LCs (DNAL1 and TECTE3), components of the docking complex (CCDC114, TTC25), and ODAassociated proteins (CCDC151, CCDC103, and ARMC4)[12,13,14,15,16,17,18,19,20,21,22] These mutations result in the complete or partial absence of the ODA, leading to PCD23. It directly binds to the β-type heavy chain (orthologous to Chlamydomonas γ heavy chain3) of the ODA in a Ca2+-dependent manner and regulates the propagation of the asymmetric flagellar wave It is necessary for changes in swimming direction during sperm chemotaxis[30] (Fig. 1a). Calaxin knockout caused a drastic loss of nodal cilia, whereas other cilia and flagella were normally formed
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