title: CaMK-II is a PKD2 target that promotes pronephric kidney development and stabilizes cilia.
abstract: 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.
authors.affiliation: Nephrology Division, Massachusetts General Hospital, Charlestown, MA 02129, USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Rothschild
authors.forename: Ludmila
authors.initials: L
authors.lastname: Francescatto
authors.forename: Iain A
authors.initials: IA
authors.lastname: Drummond
authors.forename: Robert M
authors.initials: RM
authors.lastname: Tombes
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002923:Cilia / Q000201:enzymology; D004625:Embryo, Nonmammalian / Q000201:enzymology; D004789:Enzyme Activation; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D007690:Polycystic Kidney Diseases / Q000196:embryology* / Q000201:enzymology* / Q000473:pathology; D050396:TRPP Cation Channels; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000172:deficiency / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C547527:PKD2 protein, zebrafish; D050396:TRPP Cation Channels; D029961:Zebrafish Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2