Research Explained: A complex of distal appendage-associated kinases linked to human disease regulates ciliary trafficking and stability (2021)

Authors: Abdelhalim Loukil, Chloe Barrington, and Sarah C. Goetz

Research Explained By: Sarah C. Goetz. PhD, Abdelhalim Loukil. PhD

Link to Paper: A complex of distal appendage–associated kinases linked to human disease regulates ciliary trafficking and stability | PNAS

Research Explained Summary:

Primary cilia are tiny projections present the surface of our cells that act like an antenna: They help cells receive signals from their surroundings and respond by activating certain cellular programs. These programs are important to control the development of embryos and the functioning of tissues in the human body. Because of this, genetic changes that cause defects in the structure of cilia lead to many different human genetic disorders.

The cilium assembles from an organelle called the centrosome, which forms the base of the cilium. Surprisingly, we found that CSNK2A1 is enriched at the base of the cilium, implicating it in the regulation or functioning of cilia. We found that the deletion of the CSNK2A1 gene from cells causes structural defects in the cilia: they become abnormally long and break more easily at the tip, which makes them less stable. Altogether, we found that CSNK2A1 is critical to maintaining normal movement of cellular materials inside the cilium, and for preserving the stable structure of cilia.

We also tested whether the changes to CSNK2A1 that are linked with Okur-Chung neurodevelopmental disorder (OCNDS) might affect cilia. When we introduced known CSNK2A1 mutations into cells, this led to abnormal cilia shape, suggesting the OCNDS changes might interfere with the functioning of cilia. These findings highlight a potential linkage between CSNK2A1 function in regulating cilia and OCNDS. Our ongoing work will further describe this link and uncover its molecular basis.