PUBLICATION
Overlapping and Opposing Functions of GRK2 and GRK5 during Heart Development
- Authors
- Philipp, M., Berger, I.M., Just, S., Caron, M.G.
- ID
- ZDB-PUB-140812-18
- Date
- 2014
- Source
- The Journal of biological chemistry 289(38): 26119-30 (Journal)
- Registered Authors
- Berger, Ina, Just, Steffen, Philipp, Melanie
- Keywords
- G protein-coupled receptor kinase, Hedgehog signaling pathway, cardiac development, cardiovascular, cell signaling, heart development, zebrafish
- MeSH Terms
-
- Animals
- Cell Proliferation
- Embryonic Stem Cells/physiology
- G-Protein-Coupled Receptor Kinase 2/physiology*
- G-Protein-Coupled Receptor Kinase 5/physiology*
- Gene Knockdown Techniques
- Heart/embryology*
- Heart/growth & development
- Heart Rate
- Hedgehog Proteins/metabolism
- Morpholinos/genetics
- Myocardial Contraction
- Myocardium/cytology
- Myocardium/enzymology
- Neovascularization, Physiologic
- Organ Size
- Organogenesis
- Signal Transduction
- Zebrafish
- Zebrafish Proteins/physiology*
- PubMed
- 25104355 Full text @ J. Biol. Chem.
Citation
Philipp, M., Berger, I.M., Just, S., Caron, M.G. (2014) Overlapping and Opposing Functions of GRK2 and GRK5 during Heart Development. The Journal of biological chemistry. 289(38):26119-30.
Abstract
G protein-coupled receptor kinases 2 (GRK2) and 5 (GRK5) are fundamental regulators of cardiac performance in adults, but are less well characterized for their function in the hearts of embryos. GRK2 and 5 belong to different subfamilies and function as competitors in the control of certain receptors and signaling pathways. In this study we used zebrafish to investigate whether the fish homologs of GRKs 2 and 5, Grk2/3 and Grk5, also have unique, complementary, or competitive roles during heart development. We found that they differentially regulate the heart rate of early embryos, equally facilitate heart function in older embryos, and that both are required to develop proper cardiac morphology. A loss of Grk2/3 results in dilated atria and hypoplastic ventricles, and the hearts of embryos depleted in Grk5 present with a generalized atrophy. This Grk5 morphant phenotype was associated with an overall decrease of early cardiac progenitors as well as a reduction in the area occupied by myocardial progenitor cells. In the case of Grk2/3 the progenitor decrease was confined to a subset of precursor cells with a committed ventricular fate. We attempted to rescue the GRK loss-of-function (LOF) heart phenotypes by downstream activation of Hedgehog signaling. The Grk2/3 LOF embryos were rescued by this approach, but Grk5 embryos failed to respond. In summary, we found that GRK2 and GRK5 control cardiac function as well as morphogenesis during development, although with different morphological outcomes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping