CaMK-II is a PKD2 target that promotes pronephric kidney development and stabilizes cilia
- Authors
- Rothschild, S.C., Francescatto, L., Drummond, I.A., and Tombes, R.M.
- ID
- ZDB-PUB-110719-12
- Date
- 2011
- Source
- Development (Cambridge, England) 138(16): 3387-97 (Journal)
- Registered Authors
- Drummond, Iain, Francescatto, Ludmila, Rothschild, Sarah Chase, Tombes, Robert M.
- Keywords
- none
- MeSH Terms
-
- Polycystic Kidney Diseases/embryology*
- Polycystic Kidney Diseases/enzymology*
- Polycystic Kidney Diseases/pathology
- Cilia/enzymology
- Zebrafish Proteins/deficiency
- Zebrafish Proteins/metabolism*
- Embryo, Nonmammalian/enzymology
- Enzyme Activation
- Animals
- Gene Expression Regulation, Developmental
- Carrier Proteins/metabolism*
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism*
- Gene Expression Regulation, Enzymologic
- Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics
- Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism*
- PubMed
- 21752935 Full text @ Development
Intracellular Ca2+ signals influence gastrulation, neurogenesis and organogenesis through pathways that are still being defined. One potential Ca2+ mediator of many of these morphogenic processes is CaMK-II, a conserved calmodulin-dependent protein kinase. Prolonged Ca2+ stimulation converts CaMK-II into an activated state that, in the zebrafish, is detected in the forebrain, ear and kidney. Autosomal dominant polycystic kidney disease has been linked to mutations in the Ca2+-conducting TRP family member PKD2, the suppression of which in vertebrate model organisms results in kidney cysts. Both PKD2-deficient and CaMK-II-deficient zebrafish embryos fail to form pronephric ducts properly, and exhibit anterior cysts and destabilized cloacal cilia. PKD2 suppression inactivates CaMK-II in pronephric cells and cilia, whereas constitutively active CaMK-II restores pronephric duct formation in pkd2 morphants. PKD2 and CaMK-II deficiencies are synergistic, supporting their existence in the same genetic pathway. We conclude that CaMK-II is a crucial effector of PKD2 Ca2+ that both promotes morphogenesis of the pronephric kidney and stabilizes primary cloacal cilia.