Regulation of the epithelial Na+ channel (ENaC) by phosphatidylinositides
| Autor: | Alexander Staruschenko, He-Ping Ma, Qiusheng Tong, Oleh Pochynyuk, James D. Stockand |
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| Rok vydání: | 2006 |
| Předmět: |
Epithelial sodium channel
Phosphatidylinositol 4 5-Diphosphate Cell signaling Binding Sites biology urogenital system Physiology respiratory system Receptor tyrosine kinase Sodium Channels Cell biology chemistry.chemical_compound Phosphatidylinositol 4 5-bisphosphate chemistry Phosphatidylinositol Phosphates Second messenger system biology.protein Humans Channel (broadcasting) Epithelial Sodium Channels Ion Channel Gating hormones hormone substitutes and hormone antagonists Acid-sensing ion channel |
| Zdroj: | American journal of physiology. Renal physiology. 290(5) |
| ISSN: | 1931-857X |
| Popis: | The epithelial Na+ channel (ENaC) is an end-effector of diverse cellular signaling cascades, including those with phosphatidylinositide second messengers. Recent evidence also suggests that in some instances, phospatidylinositides can directly interact with ENaC to increase channel activity by increasing channel open probability and/or membrane localization. We review here findings relevant to regulation of ENaC by phosphatidylinositol 4,5- bisphosphate (PIP2) and phosphatidylinositol 3,4,5-triphosphate (PIP3). Similar to its actions on other ion channels, PIP2 is permissive for ENaC openings having a direct effect on gating. The PIP2 binding site in ENaC involved in this regulation is most likely localized to the NH2 terminus of β-ENaC. PIP3 also affects ENaC gating but, rather than being permissive, augments open probability. The PIP3 binding site in ENaC involved in this regulation is localized to the proximal region of the COOH terminus of γ-ENaC just following the second transmembrane domain. In complementary pathways, PIP3 also impacts ENaC membrane levels through both direct actions on the channel and via a signaling cascade involving phosphoinositide 3-OH kinase (PI3-K) and the aldosterone-induced gene product serum and glucocorticoid-inducible kinase. The putative PIP3 binding site in ENaC involved in direct regulation of channel membrane levels has not yet been identified. |
| Databáze: | OpenAIRE |
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