Rothschild, S.C., Francescatto, L., Drummond, I.A., and Tombes, R.M. (2011) CaMK-II is a PKD2 target that promotes pronephric kidney development and stabilizes cilia. Development (Cambridge, England). 138(16):3387-97.
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.