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

Andrea Bieder; Gayathri Chandrasekar; Arpit Wason; Steffen Erkelenz; Jay Gopalakrishnan; Juha Kere; Isabel Tapia-Páez

doi:10.1186/s12860-023-00483-4

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

BMC Mol Cell Biol. 2023 May 26;24(1):20. doi: 10.1186/s12860-023-00483-4.

Authors

Andrea Bieder¹, Gayathri Chandrasekar¹, Arpit Wason², Steffen Erkelenz³, Jay Gopalakrishnan³, Juha Kere^{1

4}, Isabel Tapia-Páez⁵

Affiliations

¹ Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
² Center for Molecular Medicine, Institute for Biochemistry I of the University of Cologne, Cologne, Germany.
³ Institute of Human Genetics, Universitätsklinikum, Heinrich Heine University, Düsseldorf, Germany.
⁴ Molecular Neurology Research Program, University of Helsinki, Folkhälsan Institute of Genetics, Helsinki, Finland.
⁵ Department of Medicine, Solna, Karolinska Institutet, Solnavägen 30, SE-171 76, Solna, Sweden. isabel.tapia@ki.se.

Abstract

Background: DYX1C1 (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.

Results: Here, 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.

Conclusions: In 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.

Keywords: Centrosome; Cilia; Dyslexia; Genetic interaction; Zebrafish.

MeSH terms

Animals
Cell Movement / genetics
Cilia* / pathology
Gene Expression Regulation
Molecular Chaperones* / genetics
Phenotype
Zebrafish Proteins* / genetics
Zebrafish* / genetics

Substances

dnaaf4 protein, zebrafish
Molecular Chaperones
Zebrafish Proteins