Genetic and protein interaction studies between the ciliary dyslexia candidate genes DYX1C1 and DCDC2

BMC Molecular and Cell Biology

Research Article

Arpit Wason¹  Gayathri Chandrasekar²  Andrea Bieder²  Juha Kere³  Isabel Tapia-Páez⁴  Jay Gopalakrishnan⁵  Steffen Erkelenz⁵ 

[1] Center for Molecular Medicine, Institute for Biochemistry I of the University of Cologne, Cologne, Germany;Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden;Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden;Molecular Neurology Research Program, University of Helsinki, Folkhälsan Institute of Genetics, Helsinki, Finland;Department of Medicine, Solna, Karolinska Institutet, Solnavägen 30, SE-171 76, Solna, Sweden;Institute of Human Genetics, Universitätsklinikum, Heinrich Heine University, Düsseldorf, Germany;

关键词: Cilia;    Centrosome;    Dyslexia;    Genetic interaction;    Zebrafish;   

DOI  :  10.1186/s12860-023-00483-4

 received in 2022-11-17, accepted in 2023-05-09,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundDYX1C1 (DNAAF4) and DCDC2 are two of the most replicated dyslexia candidate genes in genetic studies. They both have demonstrated roles in neuronal migration, in cilia growth and function and they both are cytoskeletal interactors. In addition, they both have been characterized as ciliopathy genes. However, their exact molecular functions are still incompletely described. Based on these known roles, we asked whether DYX1C1 and DCDC2 interact on the genetic and the protein level.ResultsHere, we report the physical protein-protein interaction of DYX1C1 and DCDC2 as well as their respective interactions with the centrosomal protein CPAP (CENPJ) on exogenous and endogenous levels in different cell models including brain organoids. In addition, we show a synergistic genetic interaction between dyx1c1 and dcdc2b in zebrafish exacerbating the ciliary phenotype. Finally, we show a mutual effect on transcriptional regulation among DYX1C1 and DCDC2 in a cellular model.ConclusionsIn summary, we describe the physical and functional interaction between the two genes DYX1C1 and DCDC2. These results contribute to the growing understanding of the molecular roles of DYX1C1 and DCDC2 and set the stage for future functional studies.

【 授权许可】

CC BY   
© The Author(s) 2023

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