The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision.
Chrystal PW., Lambacher NJ., Doucette LP., Bellingham J., Schiff ER., Noel NCL., Li C., Tsiropoulou S., Casey GA., Zhai Y., Nadolski NJ., Majumder MH., Tagoe J., D'Esposito F., Cordeiro MF., Downes S., Clayton-Smith J., Ellingford J., Genomics England Research Consortium None., Mahroo OA., Hocking JC., Cheetham ME., Webster AR., Jansen G., Blacque OE., Allison WT., Au PYB., MacDonald IM., Arno G., Leroux MR.
Motile and non-motile cilia are associated with mutually-exclusive genetic disorders. Motile cilia propel sperm or extracellular fluids, and their dysfunction causes primary ciliary dyskinesia. Non-motile cilia serve as sensory/signalling antennae on most cell types, and their disruption causes single-organ ciliopathies such as retinopathies or multi-system syndromes. CFAP20 is a ciliopathy candidate known to modulate motile cilia in unicellular eukaryotes. We demonstrate that in zebrafish, cfap20 is required for motile cilia function, and in C. elegans, CFAP-20 maintains the structural integrity of non-motile cilia inner junctions, influencing sensory-dependent signalling and development. Human patients and zebrafish with CFAP20 mutations both exhibit retinal dystrophy. Hence, CFAP20 functions within a structural/functional hub centered on the inner junction that is shared between motile and non-motile cilia, and is distinct from other ciliopathy-associated domains or macromolecular complexes. Our findings suggest an uncharacterised pathomechanism for retinal dystrophy, and potentially for motile and non-motile ciliopathies in general.