Deisl Christine, Anderegg Manuel, Albano Giuseppe, Lüscher Benjamin, Cerny David, Soria Rodrigo, Bouillet Elisa, Rimoldi Stefano, Scherrer Urs, Fuster Daniel (2016), Loss of Sodium/Hydrogen Exchanger NHA2 Exacerbates Obesity- and Aging-Induced Glucose Intolerance in Mice., in
Plos one, e0163568.
Dhayat N., Simonin A., Anderegg M., Pathare G., Lu scher B. P., Deisl C., Albano G., Mordasini D., Hediger M. A., Surbek D. V., Vogt B., Sass J. O., Kloeckener-Gruissem B., Fuster D. G. (2016), Mutation in the Monocarboxylate Transporter 12 Gene Affects Guanidinoacetate Excretion but Does Not Cause Glucosuria, in
Journal of the American Society of Nephrology, 27(5), 1426-1436.
Dhayat Nasser, Schaller Andre, Albano Giuseppe, Poindexter John, Griffith Carolyn, Pasch Andreas, Gallati Sabina, Vogt Bruno, Moe Orson, Daniel Fuster (2016), The Vacuolar H+-ATPase B1 Subunit Polymorphism p.E161K Associates with Impaired Urinary Acidification in Recurrent Stone Formers, in
JASN, 1544-1554.
Albano Giuseppe, Moor Matthias, Dolder Silvia, Siegrist Mark, Wagner Carsten A., Biber Jürg, Hernando Nati, Hofstetter Willy, Bonny Olivier, Fuster Daniel G. (2015), Sodium-Dependent Phosphate Transporters in Osteoclast Differentiation and Function, in
PLOS ONE, 10(4), e0125104-e0125104.
Fuster Daniel, Alexander Todd (2014), Traditional and emerging roles for the SLC9 Na+/H+ exchangers, in
Pfluger Arch, 466(1), 61-76.
Donowitz M, Ming Tse C, Fuster D (2013), SLC9/NHE gene family, a plasma membrane and organellar family of Na +/H+ exchangers, in
Molecular Aspects of Medicine, 34(2-3), 236-251.
Deisl Christine, Simonin Alexandre, Anderegg Manuel, Albano Giuseppe, Kovacs Gergely, Ackermann Daniel, Moch Holger, Dolci Wanda, Thorens Bernard, A Hediger Matthias, Fuster Daniel G (2013), Sodium/hydrogen exchanger NHA2 is critical for insulin secretion in β-cells., in
Proceedings of the National Academy of Sciences of the United States of America, 110(24), 10004-9.
Arampatzis S, Fuster DG (2012), Gangrene and osteolysis in pancreatic insufficiency, in
Kidney International, 82(3), 364-364.
Bobulescu Ion Alexandru, Quinones Henry, Gisler Serge M., Di Sole Francesca, Shi Mingjun, Hu Ming-Chang, Zhang Jianning, Fuster Daniel, Mumby Marc, Moe Orson (2011), Dopamine inhibits the Na+/H+ Exchanger NHE3 via Protein Phosphatase 2A, in
Am J Physiol Renal Physiol, 24(298(5)), F1205-F1213.
Simonin Alexandre, Fuster Daniel (2011), Nedd4-1 and beta-Arrestin-1 Are Key Regulators of Na+/H+ Exchanger 1 Ubiquitylation, Endocytosis, and Function, in
JOURNAL OF BIOLOGICAL CHEMISTRY, 285(49), 38293-38303.
Hofstetter Willy, Siegrist Mark, Simonin Alexandre, Bonny Olivier, Fuster Daniel G. (2011), Sodium/hydrogen exchanger NHA2 in osteoclasts: Subcellular localization and role in vitro and in vivo, in
BONE, 47(2), 331-340.
Deisl Christine, Albano Giuseppe, Fuster Daniel, Role of Na/H exchange in insulin secretion by islet cells, in
Curr Opin Nephrol Hypertens, Epub ahead of print, Epub ahead.
Na+/H+ exchangers (NHEs) are ubiquitous ion transporters present in lipid bilayers in simple prokaryotes and eukaryotes, including plants, fungi and animals which harness the electrochemical gradient of one ion to energize the uphill transport of the other. In mammals, 12 NHE isoforms have been cloned so far, including plasmalemmal NHE1-5, intracellular NHE6-9, a sperm specific plasmalemmal NHE and two recently cloned evolutionarily very conserved NHEs, named NHA1 and NHA2 (or alternatively NHEDC1 and NHEDC2, respectively). NHAs belong to a new family of conserved metazoan NHEs that resemble more prokaryotic NHEs than the currently known eukaryotic NHEs. While NHA1 seems to be a gonad specific protein, NHA2 is expressed ubiquitously. However, within individual tissues, NHA2 is found only in a subset of specialized cells. Examples include osteoclasts in the bone, insulin secreting ß-cells of the pancreas, distal tubular cells of the kidney, neurons in the brain or chromaffine cells of the adrenal medulla. Based on the expression pattern, transport characteristics and genomic localization, NHA2 most likely represents the long sought Na+/Li+ countertransporter that was linked to the pathogenesis of diabetes mellitus and arterial hypertension in retro- and prospective studies. Currently, however, NHA2 kinetics as well as the biological role of NHA2 remain obscure.Based on published studies and our preliminary data, we hypothesize that mammalian NHA2 is a bona fide NHE that plays an important role in insulin secretion, renal Na+, Ca++ and acid-base homeostasis, blood pressure regulation as well as possibly bone turnover. It is the goal of this proposal to rigorously test the above mentioned hypotheses, thereby exploring the biological role of NHA2. This will be achieved by a multidisciplinary approach as follows:1.In vivo: Detailed phenotype characterization of NHA2 knock-out mice with focus on bone, endocrine pancreas, kidney and blood pressure regulation.2.In vitro: Extension of in vivo animal studies through analysis of the biological function of NHA2 on a cellular and molecular level. 3.Detailed characterization of NHA2 kinetics with fluorometry-based techniques and electrophysiological assays in different expression systems.We are convinced that, in the light of our promising preliminary data and multifaceted approach, our proposal will have a high chance of success in de-orphanizing NHA2 and elucidating its role in mammalian biology. Research on NHA2 will likely shed light on the pathogenesis of arterial hypertension, diabetes mellitus and osteoporosis, diseases, which pose a major burden to our society.