Genetic and protein interaction studies between the ciliary dyslexia candidate genes DYX1C1 and DCDC2
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 a...
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | BMC Molecular and Cell Biology |
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| Online Access: | https://doi.org/10.1186/s12860-023-00483-4 |
| _version_ | 1797817702157385728 |
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| author | Andrea Bieder Gayathri Chandrasekar Arpit Wason Steffen Erkelenz Jay Gopalakrishnan Juha Kere Isabel Tapia-Páez |
| author_facet | Andrea Bieder Gayathri Chandrasekar Arpit Wason Steffen Erkelenz Jay Gopalakrishnan Juha Kere Isabel Tapia-Páez |
| author_sort | Andrea Bieder |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T08:57:20Z |
| format | Article |
| id | doaj.art-5a629c5f0dd84427b3b6480a114b3a49 |
| institution | Directory Open Access Journal |
| issn | 2661-8850 |
| language | English |
| last_indexed | 2024-03-13T08:57:20Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Molecular and Cell Biology |
| spelling | doaj.art-5a629c5f0dd84427b3b6480a114b3a492023-05-28T11:30:54ZengBMCBMC Molecular and Cell Biology2661-88502023-05-0124111110.1186/s12860-023-00483-4Genetic and protein interaction studies between the ciliary dyslexia candidate genes DYX1C1 and DCDC2Andrea Bieder0Gayathri Chandrasekar1Arpit Wason2Steffen Erkelenz3Jay Gopalakrishnan4Juha Kere5Isabel Tapia-Páez6Department of Biosciences and Nutrition, Karolinska InstitutetDepartment of Biosciences and Nutrition, Karolinska InstitutetCenter for Molecular Medicine, Institute for Biochemistry I of the University of CologneInstitute of Human Genetics, Universitätsklinikum, Heinrich Heine UniversityInstitute of Human Genetics, Universitätsklinikum, Heinrich Heine UniversityDepartment of Biosciences and Nutrition, Karolinska InstitutetDepartment of Medicine, Solna, Karolinska InstitutetAbstract 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.https://doi.org/10.1186/s12860-023-00483-4CiliaCentrosomeDyslexiaGenetic interactionZebrafish |
| spellingShingle | Andrea Bieder Gayathri Chandrasekar Arpit Wason Steffen Erkelenz Jay Gopalakrishnan Juha Kere Isabel Tapia-Páez Genetic and protein interaction studies between the ciliary dyslexia candidate genes DYX1C1 and DCDC2 BMC Molecular and Cell Biology Cilia Centrosome Dyslexia Genetic interaction Zebrafish |
| title | Genetic and protein interaction studies between the ciliary dyslexia candidate genes DYX1C1 and DCDC2 |
| title_full | Genetic and protein interaction studies between the ciliary dyslexia candidate genes DYX1C1 and DCDC2 |
| title_fullStr | Genetic and protein interaction studies between the ciliary dyslexia candidate genes DYX1C1 and DCDC2 |
| title_full_unstemmed | Genetic and protein interaction studies between the ciliary dyslexia candidate genes DYX1C1 and DCDC2 |
| title_short | Genetic and protein interaction studies between the ciliary dyslexia candidate genes DYX1C1 and DCDC2 |
| title_sort | genetic and protein interaction studies between the ciliary dyslexia candidate genes dyx1c1 and dcdc2 |
| topic | Cilia Centrosome Dyslexia Genetic interaction Zebrafish |
| url | https://doi.org/10.1186/s12860-023-00483-4 |
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