Bibliographic Details
| Title: |
A zebrafish forward genetic screen identifies an indispensable threonine residue in the kinase domain of PRKD2 |
| Authors: |
Panagiota Giardoglou, Despina Bournele, Misun Park, Stavroula Kanoni, George V. Dedoussis, Susan F. Steinberg, Panos Deloukas, Dimitris Beis |
| Source: |
Biology Open, Vol 10, Iss 3 (2021) |
| Publisher Information: |
The Company of Biologists, 2021. |
| Publication Year: |
2021 |
| Collection: |
LCC:Science
LCC:Biology (General) |
| Subject Terms: |
protein kinase d2, cardiovascular development, cardiac valves, zebrafish, Science, Biology (General), QH301-705.5 |
| More Details: |
Protein kinase D2 belongs to a family of evolutionarily conserved enzymes regulating several biological processes. In a forward genetic screen for zebrafish cardiovascular mutants, we identified a mutation in the prkd2 gene. Homozygous mutant embryos develop as wild type up to 36 h post-fertilization and initiate blood flow, but fail to maintain it, resulting in a complete outflow tract stenosis. We identified a mutation in the prkd2 gene that results in a T757A substitution at a conserved residue in the kinase domain activation loop (T714A in human PRKD2) that disrupts catalytic activity and drives this phenotype. Homozygous mutants survive without circulation for several days, allowing us to study the extreme phenotype of no intracardiac flow, in the background of a functional heart. We show dysregulation of atrioventricular and outflow tract markers in the mutants and higher sensitivity to the Calcineurin inhibitor, Cyclosporin A. Finally we identify TBX5 as a potential regulator of PRKD2. Our results implicate PRKD2 catalytic activity in outflow tract development in zebrafish. This article has an associated First Person interview with the first author of the paper. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2046-6390 |
| Relation: |
http://bio.biologists.org/content/10/3/bio058542; https://doaj.org/toc/2046-6390 |
| DOI: |
10.1242/bio.058542 |
| Access URL: |
https://doaj.org/article/fdda6340f7e84714ac365317171e3ccf |
| Accession Number: |
edsdoj.fdda6340f7e84714ac365317171e3ccf |
| Database: |
Directory of Open Access Journals |
