Rapid translocation and insertion of the epithelial Na+ channel in response to RhoA signaling. J Biol Chem 2006 Sep 08;281(36):26520-7
Date
07/11/2006Pubmed ID
16829523DOI
10.1074/jbc.M603716200Scopus ID
2-s2.0-33748746597 (requires institutional sign-in at Scopus site) 60 CitationsAbstract
Activity of the epithelial Na+ channel (ENaC) is limiting for Na+ absorption across many epithelia. Consequently, ENaC is a central effector impacting systemic blood volume and pressure. Two members of the Ras superfamily of small GTPases, K-Ras and RhoA, activate ENaC. K-Ras activates ENaC via a signaling pathway involving phosphatidylinositol 3-kinase and production of phosphatidylinositol 3,4,5-trisphosphate with the phospholipid directly interacting with the channel to increase open probability. How RhoA increases ENaC activity is less clear. Here we report that RhoA and K-Ras activate ENaC through independent signaling pathways and final mechanisms of action. Activation of RhoA signaling rapidly increases the membrane levels of ENaC likely by promoting channel insertion. This process dramatically increases functional ENaC current, resulting in tight spatial-temporal control of these channels. RhoA signals to ENaC via a transduction pathway, including the downstream effectors Rho kinase and phosphatidylinositol-4-phosphate 5-kinase. Phosphatidylinositol 4,5-biphosphate produced by activated phosphatidylinositol 4-phosphate 5-kinase may play a role in targeting vesicles containing ENaC to the plasma membrane.
Author List
Pochynyuk O, Medina J, Gamper N, Genth H, Stockand JD, Staruschenko AMESH terms used to index this publication - Major topics in bold
AnimalsCHO Cells
COS Cells
Cell Membrane
Cricetinae
Epithelial Sodium Channels
Genes, ras
Patch-Clamp Techniques
Phosphatidylinositol 3-Kinases
Phosphatidylinositol 4,5-Diphosphate
Phosphotransferases (Alcohol Group Acceptor)
Recombinant Fusion Proteins
Signal Transduction
rho GTP-Binding Proteins
rhoA GTP-Binding Protein
