A complex of distal appendage–associated kinases linked to human disease regulates ciliary trafficking and stability
Abdelhalim Loukil, Chloe Barrington, Sarah C. Goetz
Abstract
Significance Primary cilia (PC) are sensory organelles essential for the development and maintenance of adult tissues. Accordingly, dysfunction of PC causes human disorders called ciliopathies. Hence, a thorough understanding of the molecular regulation of PC is critical. Our findings highlight CSNK2A1 as a modulator of cilia trafficking and stability, tightly related to TTBK2 function. Enriched at the centrosome, CSNK2A1 prevents abnormal accumulation of key ciliary proteins, instability at the tip, and aberrant activation of the Sonic Hedgehog pathway. Furthermore, we establish that Csnk2a1 mutations associated with Okur-Chung neurodevelopmental disorder (OCNDS) alter cilia morphology. Thus, we report a potential linkage between CSNK2A1 ciliary function and OCNDS.