ArticleThe Journal of biological chemistry2014
Hypotonicity stimulates potassium flux through the WNK-SPAK/OSR1 kinase cascade and the Ncc69 sodium-potassium-2-chloride cotransporter in the Drosophila renal tubule.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 48 citations in OpenAlex.
- Molecular and neural mechanisms of sodium sensation.Genes & genomics · 2026Review
- Calcium-binding protein 39 in with-no-lysine kinase signaling and the modulation of renal tubular transport.Current opinion in nephrology and hypertension · 2025Review
- Function and regulation of the insect NaCCC2 sodium transport proteins.Comparative biochemistry and physiology. Part A, Molecular & integrative physiology · 2024Article
- Circadian Rhythm Regulation by Pacemaker Neuron Chloride Oscillation in Flies.Physiology (Bethesda, Md.) · 2024Review
- Physiological roles of chloride ions in bodily and cellular functions.The journal of physiological sciences : JPS · 2023Review
- Mechanical stimulation from the surrounding tissue activates mitochondrial energy metabolism in Drosophila differentiating germ cells.Developmental cell · 2023Article
- Hydrostatic Pressure Sensing by WNK kinases.Molecular biology of the cell · 2023Article
- Unanticipated domain requirements for Drosophila Wnk kinase in vivo.PLoS genetics · 2023Article
- Review
- SIK3 and Wnk converge on Fray to regulate glial K+ buffering and seizure susceptibility.PLoS genetics · 2023Article
- Article
- Drosophila melanogaster: a simple genetic model of kidney structure, function and disease.Nature reviews. Nephrology · 2022Review
- UBR5 is a novel regulator of WNK1 stability.American journal of physiology. Cell physiology · 2022Article
- Sequence analysis and function of mosquito aeCCC2 and Drosophila Ncc83 orthologs.Insect biochemistry and molecular biology · 2022Article
- Chloride oscillation in pacemaker neurons regulates circadian rhythms through a chloride-sensing WNK kinase signaling cascade.Current biology : CB · 2022Article
- Updates on ion and water transport by the Malpighian tubule.Current opinion in insect science · 2021Review
- WNKs are potassium-sensitive kinases.American journal of physiology. Cell physiology · 2021Article
- The septate junction protein Mesh is required for epithelial morphogenesis, ion transport, and paracellular permeability in theAmerican journal of physiology. Cell physiology · 2020Article
- Physiology, Development, and Disease Modeling in theGenetics · 2020Review
- The Drosophila Malpighian tubule as a model for mammalian tubule function.Current opinion in nephrology and hypertension · 2019Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The ability to osmoregulate is fundamental to life. Adult Drosophila melanogaster maintain hemolymph osmolarity within a narrow range. Osmolarity modulates transepithelial ion and water flux in the Malpighian (renal) tubules of the fly, which are in direct contact with hemolymph in vivo, but the mechanisms causing increased transepithelial flux in response to hypotonicity are unknown. Fly renal tubules secrete a KCl-rich fluid. We have previously demonstrated a requirement for Ncc69, the fly sodium-potassium-2-chloride cotransporter (NKCC), in tubule K(+) secretion. Mammalian NKCCs are regulated by a kinase cascade consisting of the with-no-lysine (WNK) and Ste20-related proline/alanine-rich (SPAK)/oxidative stress response (OSR1) kinases. Here, we show that decreasing Drosophila WNK activity causes a reduction in K(+) flux. Similarly, knocking down the SPAK/OSR1 homolog fray also decreases K(+) flux. We demonstrate that a hierarchical WNK-Fray signaling cascade regulates K(+) flux through Ncc69, because (i) a constitutively active Fray mutant rescues the wnk knockdown phenotype, (ii) Fray directly phosphorylates Ncc69 in vitro, and (iii) the effect of wnk and fray knockdown is abolished in Ncc69 mutants. The stimulatory effect of hypotonicity on K(+) flux is absent in wnk, fray, or Ncc69 mutant tubules, suggesting that the Drosophila WNK-SPAK/OSR1-NKCC cascade is an essential molecular pathway for osmoregulation, through its effect on transepithelial ion flux and fluid generation by the renal tubule.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.