학술논문
The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision
Document Type
Original Paper
Author
Chrystal, Paul W.; Lambacher, Nils J.; Doucette, Lance P.; Bellingham, James; Schiff, Elena R.; Noel, Nicole C. L.; Li, Chunmei; Tsiropoulou, Sofia; Casey, Geoffrey A.; Zhai, Yi; Nadolski, Nathan J.; Majumder, Mohammed H.; Tagoe, Julia; D’Esposito, Fabiana; Cordeiro, Maria Francesca; Downes, Susan; Clayton-Smith, Jill; Ellingford, Jamie; Mahroo, Omar A.; Hocking, Jennifer C.; Cheetham, Michael E.; Webster, Andrew R.; Jansen, Gert; Blacque, Oliver E.; Allison, W. Ted; Au, Ping Yee Billie; MacDonald, Ian M.; Arno, Gavin; Leroux, Michel R.
Source
Nature Communications. 13(1)
Subject
Language
English
ISSN
2041-1723
Abstract
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.
Motile and non-motile cilia have distinct functions and protein complexes associated with them. Here, the authors show the conserved protein CFAP20 is important for both motile and non-motile cilia and is distinct from other ciliopathy-associated domains or macromolecular complexes.
Motile and non-motile cilia have distinct functions and protein complexes associated with them. Here, the authors show the conserved protein CFAP20 is important for both motile and non-motile cilia and is distinct from other ciliopathy-associated domains or macromolecular complexes.