Ttc30a affects tubulin modifications in a model for ciliary chondrodysplasia with polycystic kidney disease
Maike Getwan, Anselm Hoppmann, Pascal Schlosser, Kelli Grand, Weiting Song, R. Diehl, Sophie Schroda, Florian Heeg, Konstantin Deutsch, Friedhelm Hildebrandt, Ekkehart Lausch, Anna Köttgen, Soeren S. Lienkamp
Abstract
Significance Cilia are tubulin-based cellular appendages, and their dysfunction has been linked to a variety of genetic diseases. Ciliary chondrodysplasia is one such condition that can co-occur with cystic kidney disease and other organ manifestations. We modeled skeletal ciliopathies by mutating two established disease genes in Xenopus tropicalis frogs. Bioinformatic analysis identified ttc30a as a ciliopathy network component, and targeting it replicated skeletal malformations and renal cysts as seen in patients and the amphibian models. A loss of Ttc30a affected cilia by altering posttranslational tubulin modifications. Our findings identify TTC30A/B as a component of ciliary segmentation essential for cartilage differentiation and renal tubulogenesis. These findings may lead to novel therapeutic targets in treating ciliary skeletopathies and cystic kidney disease.