ArticleProceedings of the National Academy of Sciences of the United States of America2005
Rho GTPases dictate the mobility of the Na/H exchanger NHE3 in epithelia: role in apical retention and targeting.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 59 citations in OpenAlex.
- Structural basis of autoinhibition of the human NHE3-CHP1 complex.Science advances · 2022Article
- The Role of Plasma Membrane Sodium/Hydrogen Exchangers in Gastrointestinal Functions: Proliferation and Differentiation, Fluid/Electrolyte Transport and Barrier Integrity.Frontiers in physiology · 2022Review
- The recycling regulation of sodium-hydrogen exchanger isoform 3(NHE3) in epithelial cells.Cell cycle (Georgetown, Tex.) · 2021Review
- High-mobility group box 1 inhibits HCO3- absorption in the medullary thick ascending limb through RAGE-Rho-ROCK-mediated inhibition of basolateral Na+/H+ exchange.American journal of physiology. Renal physiology · 2016Article
- Carbonic anhydrase II binds to and increases the activity of the epithelial sodium-proton exchanger, NHE3.American journal of physiology. Renal physiology · 2015Article
- Sorting nexin 27 regulates basal and stimulated brush border trafficking of NHE3.Molecular biology of the cell · 2015Article
- The Na+/H+ Exchanger-3 (NHE3) Activity Requires Ezrin Binding to Phosphoinositide and Its Phosphorylation.PloS one · 2015Article
- Myosin VI mediates the movement of NHE3 down the microvillus in intestinal epithelial cells.Journal of cell science · 2014Article
- Lysophosphatidic acid stimulation of NHE3 exocytosis in polarized epithelial cells occurs with release from NHERF2 via ERK-PLC-PKCδ signaling.American journal of physiology. Cell physiology · 2014Article
- Unique regulation of human Na+/H+ exchanger 3 (NHE3) by Nedd4-2 ligase that differs from non-primate NHE3s.The Journal of biological chemistry · 2014Article
- Modulation of angiotensin II-induced inflammatory cytokines by the Epac1-Rap1A-NHE3 pathway: implications in renal tubular pathobiology.American journal of physiology. Renal physiology · 2014Article
- Ezrin is required for the functional regulation of the epithelial sodium proton exchanger, NHE3.PloS one · 2013Article
- Differential association of the Na+/H+ Exchanger Regulatory Factor (NHERF) family of adaptor proteins with the raft- and the non-raft brush border membrane fractions of NHE3.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2013Article
- Open conformation of ezrin bound to phosphatidylinositol 4,5-bisphosphate and to F-actin revealed by neutron scattering.The Journal of biological chemistry · 2012Article
- The epithelial sodium/proton exchanger, NHE3, is necessary for renal and intestinal calcium (re)absorption.American journal of physiology. Renal physiology · 2012Article
- Analysis of detergent-free lipid rafts isolated from CD4+ T cell line: interaction with antigen presenting cells promotes coalescing of lipid rafts.Cell communication and signaling : CCS · 2011Article
- Elevated calcium acutely regulates dynamic interactions of NHERF2 and NHE3 proteins in opossum kidney (OK) cell microvilli.The Journal of biological chemistry · 2011Article
- Membrane surface charge dictates the structure and function of the epithelial Na+/H+ exchanger.The EMBO journal · 2011Article
- Loss of PDZ-adaptor protein NHERF2 affects membrane localization and cGMP- and [Ca2+]- but not cAMP-dependent regulation of Na+/H+ exchanger 3 in murine intestine.The Journal of physiology · 2010Article
- NHE3 mobility in brush borders increases upon NHERF2-dependent stimulation by lyophosphatidic acid.Journal of cell science · 2010Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Proximal tubular reabsorption of filtered sodium by the sodium/hydrogen exchanger isoform 3 (NHE3), located on the apical membrane, is fundamental to the maintenance of systemic volume and pH homeostasis. NHE3 is finely regulated by a variety of hormones and by changes in ionic composition and volume, likely requiring redistribution of the exchangers. We analyzed the subcellular distribution and dynamics of the exchangers by generating an epithelial line expressing NHE3 tagged with an exofacial epitope, which enabled us to monitor exchanger mobility and traffic in intact cells. Using determinations of fluorescence recovery after photobleaching in combination with dynamic measurements of subcellular distribution, we found that, in renal epithelial cells, NHE3 exists in four distinct subcompartments: a virtually immobile subpopulation that is retained on the apical membrane by interaction with the actin cytoskeleton in a manner that depends on the sustained activity of Rho GTPases; a mobile subpopulation on the apical membrane, which can be readily internalized; and two intracellular compartments that can be differentiated by their rate of exchange with the apical pool of NHE3. We provide evidence that detachment of the immobile fraction from its cytoskeletal anchorage leads to rapid internalization. These observations suggest that modulation of the mobile fraction of NHE3 on the apical membrane can alter the number of functional exchangers on the cell surface and, consequently, the rate of transepithelial ion transport. Regulation of the interaction of NHE3 with the actin cytoskeleton can therefore provide a new mode of regulation of sodium and hydrogen transport.
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Registered trials
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.