Ankyrin G Expression Regulates Apical Delivery of the Epithelial Sodium Channel (ENaC)
| Autor: | Lindsay Kightlinger, Xiaoning Liu, Christine A. Klemens, Robert S. Edinger, Michael B. Butterworth |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Epithelial sodium channel inorganic chemicals Ankyrins FOS: Basic medicine Nephron Endocytosis Biochemistry 03 medical and health sciences Mice 0302 clinical medicine Membrane Biology medicine 111601 Cell Physiology Ankyrin Animals Kidney Tubules Collecting Epithelial Sodium Channels Molecular Biology Ion transporter Cells Cultured chemistry.chemical_classification Ion Transport Reabsorption urogenital system Cell Membrane Biological Transport Cell Biology Apical membrane respiratory system Cell biology Rats Vesicular transport protein 030104 developmental biology medicine.anatomical_structure chemistry Sodium-Potassium-Exchanging ATPase 030217 neurology & neurosurgery hormones hormone substitutes and hormone antagonists |
| DOI: | 10.25376/hra.7808870.v1 |
| Popis: | The epithelial sodium channel (ENaC) is the limiting entry point for Na+ reabsorption in the distal kidney nephron and is regulated by numerous hormones, including the mineralocorticoid hormone aldosterone. Previously we identified ankyrin G (AnkG), a cytoskeletal protein involved in vesicular transport, as a novel aldosterone-induced protein that can alter Na+ transport in mouse cortical collecting duct cells. However, the mechanisms underlying AnkG regulation of Na+ transport were unknown. Here we report that AnkG expression directly regulates Na+ transport by altering ENaC activity in the apical membrane. Increasing AnkG expression increased ENaC activity while depleting AnkG reduced ENaC-mediated Na+ transport. These changes were due to a change in ENaC directly rather than through alterations to the Na+ driving force created by Na+/K+-ATPase. Using a constitutively open mutant of ENaC, we demonstrate that the augmentation of Na+ transport is caused predominantly by increasing the number of ENaCs at the surface. To determine the mechanism of AnkG action on ENaC surface number, changes in rates of internalization, recycling, and membrane delivery were investigated. AnkG did not alter ENaC delivery to the membrane from biosynthetic pathways or removal by endocytosis. However, AnkG did alter ENaC insertion from constitutive recycling pathways. These findings provide a mechanism to account for the role of AnkG in the regulation of Na+ transport in the distal kidney nephron. |
| Databáze: | OpenAIRE |
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