Ion transport, the vectorial movement of ions across cell membranes, is a fundamental process that is essential to normal physiology and is perturbed in a variety of disease processes. In the kidney, epithelial ion transport regulates the concentration of ions, such as sodium and potassium, and determines extracellular volume and blood pressure. Kidney dysfunction can lead to perturbations in these regulatory processes, resulting in electrolyte disturbances, hypotension, or hypertension.
My laboratory is interested in using the fruit fly Drosophila melanogaster as a model organism to study ion transport processes relevant to human physiology. Drosophila has a short life cycle, sophisticated genetics, and in many cases single gene representation of mammalian multi-gene families, simplifying analysis of pathways of interest. Our goal is to use to the fly to study ion transporters and channels that are conserved in humans, as well as the molecular mechanisms of regulation of these transporters and channels. One area of focus is the SLC12 family of cation-chloride transporters, such as the potassium- chloride cotransporter and the sodium-potassium-2 chloride cotransporter, and their regulation by WNK and SPAK/OSR1 kinases, which have been implicated in hypertensive disorders in humans. We are also studying inwardly rectifying potassium channels, which have also been implicated in several human disorders. We study these pathways in the fly renal tubule, in which epithelial ion transport is required for ionic and osmotic homeostasis. Additional projects study the WNK-SPAK/OSR1 pathway in circadian rhythm, as well as the role of this and other pathways in salt sensitivity. Our goal is to understand these transporters, channels and their regulation in greater mechanistic detail, identify new regulatory factors, and translate these insights into improved understanding of ion transport processes in health and disease.
- Renal Physiology
- Ion Transport
- Drosophila melanogaster
- Malpighian tubule
- Potassium homeostasis
- Electrolyte disorders
- Circadian Rhythms
- Al-Rabadi LF & Caza T, Trivin-Avillach C, Rodan AR, Andeen N, Hayashi N, Williams B, Revelo MP, Clayton F, Abraham J, Lin E, Liou W, Zou CJ, Ramkumar N, Cummins T, Wilkey DW, Kawalit I, Herzog C, Storey A, Edmondson R, Sjoberg R, Yang T, Chien J, Merchant M, Arthur J, K (2021). Serine protease HTRA1 as a novel target antigen in primary membranous nephropathy. J Am Soc Nephrol.
- Pleinis JM & Norrell L, Akella R, Humphreys JM, He H, Sun Q, Zhang F, Sosa-Pagan J, Morrison DE, Schellinger JN, Jackson LK, Goldsmith EJ, Rodan AR (2021). WNKs are potassium-sensitive kinases. Am J Physiol Cell Physiol. Vol. 320, C703-C721.
- Mishra P & Yang SE, Montgomery AB, Reed AR, Rodan AR, Rothenfluh A (2021). The fly liquid-food electroshock assay (FLEA) suggests opposite roles for neuropeptide F in avoidance of bitterness and shock. BMC Biol. Vol. 19, 31.
- Jonusaite S & Rodan AR (2021). Molecular basis for epithelial morphogenesis and ion transport in the Malpighian tubule. (pp. 7-11). Vol. 47. Curr Opin Insect Sci.
- Talsness DM & Owings KG, Coelho E, Mercenne G, Pleinis JM, Partha R, Hope KA, Zuberi AR, Clark NL, Lutz CM, Rodan AR, Chow CY (2020). A Drosophila screen identifies NKCC1 as a modifier of NGLY1 deficiency. eLife. Vol. 9, e57831.
- Beyenbach KW & Schoene F, Breitsprecher LF, Tiburcy F, Furuse M, Izumi Y, Meyer H, Rodan AR, Paululat A (2020). The septate junction protein Tetraspanin 2A is critical to the structure and function of Malpighian tubules in Drosophila melanogaster. Am J Physiol Cell Physiol. Vol. 318, C1107-C1122.
- Jonusaite S & Beyenbach KW, Meyer H, Paululat A, Izumi Y, Furuse M, Rodan AR (2020). The septate junction protein Mesh is required for epithelial morphogenesis, ion transport and paracellular permeability in the Drosophila Malpighian tubule. Am J Physiol Cell Physiol. Vol. 318, C675-C695.
- Butts AR & Ojelade SA, Pronovost ED, Seguin A, Merrill CB, Rodan AR, Rothenfluh A (2019). Altered actin filament dynamics in the Drosophila mushroom bodies lead to fast acquisition of alcohol consumption preference. J Neurosci. Vol. 39, 8877-8884.
- Rodan AR (2019). The Drosophila Malpighian tubule as a model for mammalian tubule function. (pp. 455-464). Vol. 28. Curr Opin Nephrol Hypertens.
- Rodan AR (2019). ) Intracellular chloride: a regulator of transepithelial transport in the distal nephron. (pp. 360-367). Vol. 28. Curr Opin Neph Hypertens.
- Stenesen D & Moehlman AT, Schellinger JN, Rodan AR*, Krämer H (2019). The glial sodium-potassium-2-chloride cotransporter is required for synaptic transmission in the Drosophila visual system. Sci Rep, 9: 2475. Sci Rep. Vol. 9, 2475.
- Lakshmipathi J & Wheatley W, Kumar A, Mercenne G, Rodan AR, Kohan DE (2019). Identification of NFAT5 as a transcriptional regulation of the EDN1 gene in collecting duct. J Biol Chem.
- Rodan AR (2018). Sodium and magnesium in the distal convoluted tubule: no longer a couple?. (pp. e13780). Vol. 6. Physiol Rep.
- Rodan AR (2018). WNK-SPAK/OSR1 signaling: lessons learned from an insect renal epithelium. Am J Physiol Renal Physiol.
- Sun Q & Wu Y, Jonusaite S, Pleinis JM, Humphreys JM, He H, Schellinger JN, Akella R, Stenesen D, Krämer H, Goldsmith EJ, Rodan AR (2018). Intracellular chloride and scaffold protein Mo25 cooperatively regulate transepithelial ion transport through WNK signaling in the Malpighian tubule. J Am Soc Neph. Vol. 29, 1449-1461.
- Gonzalez DA & Jia T, Pinzon JH, Acevedo SF, Ojelade SA, Xu B, Tay N, Desrivieres S, Hernandez JL, Banaschewski T, Buchel C, Bokde ALW, Conrod PJ, Flor H, Frouin V, Gallinat J, Garavan H, Gowland PA, Heinz A, Ittermann B, Lathrop M, Martinot JL, Paus T, Smolka MN, Rodan (2018). The Arf6 activator Efa6/PSD3 confers regional specificity and modulates ethanol consumption in Drosophila and humans. Mol Psychiatry. Vol. 23, 621-628.
- Shalaby NA & Pinzón JH, Narayanan A, Jin EJ, Ritz M, Dove R, Wolfenberg H, Rodan AR, Buszczak M, Rothenfluh A (2018). JmjC domain proteins modulate circadian behaviors and sleep in Drosophila. Sci Reports. Vol. 8, 815.
- Pinzón JH & Reed AR, Shalaby NA, Buszczak M, Rodan AR, Rothenfluh A (2017). Alcohol-induced behaviors require a subset of Drosophila JmjC-domain histone demethylases in the nervous system. Alcohol Clin Exp Res. Vol. 41, 2015-2024.
- Rodan AR (2017). Potassium: friend or foe?. (pp. 1109-1121). Vol. 32. Pediatr Nephrol.
- Rodan AR & Jenny A (2017). WNK kinases in development and disease. (pp. 1-47). Vol. 123. Curr Topics Dev Biol.
- Cheng CJ, Rodan AR & Huang CL (2017). Emerging Targets of Diuretic Therapy. Clinical pharmacology and therapeutics. Vol. 102, 420-435.
- Mahajan A, Rodan AR, Le TH, Gaulton KJ, Haessler J, Stilp AM, Kamatani Y, Zhu G, Sofer T, Puri S, Schellinger JN, Chu PL, Cechova S, van Zuydam N, Arnlov J, Flessner MF, Giedraitis V, Heath AC, Kubo M, Larsson A, Lindgren CM, Madden PA, Montgomery GW, Papanicolaou GJ, Reiner AP, Sundström J, Thornton TA, Lind L, Ingelsson E, Cai J, Martin NG, Kooperberg C, Matsuda K, Whitfield JB, Okada Y, Laurie CC, Morris AP, Franceschini N, & (2016). Trans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to Salt Sensitivity. American journal of human genetics. Vol. 99, 636-46.
- Acevedo SF, Peru y Colón de Portugal RL, Gonzalez DA, Rodan AR & Rothenfluh A (2015). S6 Kinase Reflects and Regulates Ethanol-Induced Sedation. The Journal of neuroscience : the official journal of the Society for Neuroscience. Vol. 35, 15396-402.
- Wu Y, Baum M, Huang CL & Rodan AR (2015). Two inwardly rectifying potassium channels, Irk1 and Irk2, play redundant roles in Drosophila renal tubule function. American journal of physiology. Regulatory, integrative and comparative physiology. Vol. 309, R747-56.
- Ojelade SA, Jia T, Rodan AR, Chenyang T, Kadrmas JL, Cattrell A, Ruggeri B, Charoen P, Lemaitre H, Banaschewski T, Büchel C, Bokde AL, Carvalho F, Conrod PJ, Flor H, Frouin V, Gallinat J, Garavan H, Gowland PA, Heinz A, Ittermann B, Lathrop M, Lubbe S, Martinot JL, Paus T, Smolka MN, Spanagel R, O'Reilly PF, Laitinen J, Veijola JM, Feng J, Desrivières S, Jarvelin MR, Schumann G, Rothenfluh A & Albrecht L (2015). Rsu1 regulates ethanol consumption in Drosophila and humans. Proceedings of the National Academy of Sciences of the United States of America. Vol. 112, E4085-93.
- Wu Y, Schellinger JN, Huang CL & Rodan AR (2014). Hypotonicity stimulates potassium flux through the WNK-SPAK/OSR1 kinase cascade and the Ncc69 sodium-potassium-2-chloride cotransporter in the Drosophila renal tubule. The Journal of biological chemistry. Vol. 289, 26131-42.
- Peru Y Colón de Portugal RL, Ojelade SA, Penninti PS, Dove RJ, Nye MJ, Acevedo SF, Lopez A, Rodan AR & Rothenfluh A (2014). Long-lasting, experience-dependent alcohol preference in Drosophila. Addiction biology. Vol. 19, 392-401.
- Peru Y Colón de Portugal RL, Acevedo SF, Rodan AR, Chang LY, Eaton BA & Rothenfluh A (2012). Adult neuronal Arf6 controls ethanol-induced behavior with Arfaptin downstream of Rac1 and RhoGAP18B. The Journal of neuroscience : the official journal of the Society for Neuroscience. Vol. 32, 17706-13.
- Rodan AR, Baum M & Huang CL (2012). The Drosophila NKCC Ncc69 is required for normal renal tubule function. American journal of physiology. Cell physiology. Vol. 303, C883-94.
- Rodan AR, Cheng CJ & Huang CL (2011). Recent advances in distal tubular potassium handling. American journal of physiology. Renal physiology. Vol. 300, F821-7.
- Rodan AR & Huang CL (2010). An emerging role for SPAK in NCC, NKCC, and blood pressure regulation. (pp. 1812-4). Vol. 21. Journal of the American Society of Nephrology : JASN.
- Rodan AR & Rothenfluh A (2010). The genetics of behavioral alcohol responses in Drosophila. International review of neurobiology. Vol. 91, 25-51.
- Rodan AR & Huang CL (2009). Distal potassium handling based on flow modulation of maxi-K channel activity. Current opinion in nephrology and hypertension. Vol. 18, 350-5.
- Corl AB, Rodan AR & Heberlein U (2004). Insulin signaling in the nervous system regulates ethanol intoxication in Drosophila melanogaster. Nature neuroscience. Vol. 8, 18-9.
- Wolf FW, Rodan AR, Tsai LT & Heberlein U (2002). High-resolution analysis of ethanol-induced locomotor stimulation in Drosophila. The Journal of neuroscience : the official journal of the Society for Neuroscience. Vol. 22, 11035-44.
- Rodan AR, Kiger JA & Heberlein U (2002). Functional dissection of neuroanatomical loci regulating ethanol sensitivity in Drosophila. The Journal of neuroscience : the official journal of the Society for Neuroscience. Vol. 22, 9490-501.
- Cheng Y, Endo K, Wu K, Rodan AR, Heberlein U & Davis RL (2001). Drosophila fasciclinII is required for the formation of odor memories and for normal sensitivity to alcohol. Cell. Vol. 105, 757-68.
- Lin K, Dorman JB, Rodan A & Kenyon C (1997). daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science (New York, N.Y.). Vol. 278, 1319-22.
- Rodan AR, Simons JF, Trombetta ES & Helenius A (1997). N-linked oligosaccharides are necessary and sufficient for association of glycosylated forms of bovine RNase with calnexin and calreticulin. The EMBO journal. Vol. 15, 6921-30.