RESEARCH EXPLAINED

A complex of distal appendage-associated kinases linked to human disease regulates ciliary trafficking and stability

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

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

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

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.

If you have any further questions, please contact Jennifer Sills at jennifer@csnk2a1foundation.org

 

 

 

Sarah C. Goetz. PhD

Sarah C. Goetz. PhD

My overarching scientific interest is in the genetic control of embryonic development and the cellular and molecular basis of developmental disorders. I received my Ph.D. in Molecular, Cellular and Developmental Biology from the University of North Carolina at Chapel Hill in 2007, studying the regulation of heart development. I then pursued postdoctoral studies with Dr. Kathryn Anderson at Sloan-Kettering Institute in New York City to study cellular signaling pathways that control the patterning of embryos, and specifically the role of primary cilia in mediating these signals. In 2015, I started my own research group at Duke University School of Medicine where we examine the signals that control the assembly of cilia and also study how dysfunction of signaling at the cilium causes or contributes to neurodevelopmental and neurodegenerative disorders.

Abdelhalim Loukil. PhD

Abdelhalim Loukil. PhD

I received my Ph.D. in 2013 from the University of Montpellier 2, France. I moved to the US in late 2013 to start my first postdoc at the University of California, Irvine to work on primary cilia biogenesis. Then, I joined Sarah Goetz’s lab in 2017 to study the effect of primary cilium dysfunctions in neurodevelopmental disorders. My long-term goal is to be an independent investigator and establish original research on the exciting roles of primary cilia in neural function and homeostasis. More specifically, my research interests implicate the understanding of the link between primary cilium dysfunction and neurodevelopmental disorders with a focus on OCNDS.

 

 

 

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