HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 36, 26520-26527, September 8, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/36/26520    most recent M603716200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pochynyuk, O. Articles by Staruschenko, A. Search for Related Content PubMed PubMed Citation Articles by Pochynyuk, O. Articles by Staruschenko, A. Social Bookmarking                      What's this?

Rapid Translocation and Insertion of the Epithelial Na⁺ Channel in Response to RhoA Signaling^*

Oleh Pochynyuk, Jorge Medina, Nikita Gamper, Harald Genth^¶, James D. Stockand¹, and Alexander Staruschenko

From the Department of Physiology, University of Texas Health Science Center, San Antonio, Texas 78229, Institute of Membrane and Systems Biology, University of Leeds, Leeds LS2 9JT, United Kingdom, and ^¶Institut fur Toxikologie, Medizinische Hochschule, D-30625 Hannover, Germany

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.

Received for publication, April 18, 2006 , and in revised form, June 12, 2006.

^* This work was supported by NIDDK Grant RO1-DK-59594 from the National Institutes of Health, American Heart Association-Texas Affiliate Grant 0355012Y (to J. D. S.), and a research fellowship from the National Kidney Foundation (to A. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Physiology, 7756, University of Texas Health Science Center, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900. Tel.: 210-567-4332; E-mail: stockand{at}uthscsa.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				V. McEneaney, B. J. Harvey, and W. Thomas Aldosterone Regulates Rapid Trafficking of Epithelial Sodium Channel Subunits in Renal Cortical Collecting Duct Cells via Protein Kinase D Activation Mol. Endocrinol., April 1, 2008; 22(4): 881 - 892. [Abstract] [Full Text] [PDF]

				O. Pochynyuk, V. Bugaj, A. Vandewalle, and J. D. Stockand Purinergic control of apical plasma membrane PI(4,5)P2 levels sets ENaC activity in principal cells Am J Physiol Renal Physiol, January 1, 2008; 294(1): F38 - F46. [Abstract] [Full Text] [PDF]

				K. M. Weixel, R. S. Edinger, L. Kester, C. J. Guerriero, H. Wang, L. Fang, T. R. Kleyman, P. A. Welling, O. A. Weisz, and J. P. Johnson Phosphatidylinositol 4-Phosphate 5-Kinase Reduces Cell Surface Expression of the Epithelial Sodium Channel (ENaC) in Cultured Collecting Duct Cells J. Biol. Chem., December 14, 2007; 282(50): 36534 - 36542. [Abstract] [Full Text] [PDF]

				C.-L. Huang Complex roles of PIP2 in the regulation of ion channels and transporters Am J Physiol Renal Physiol, December 1, 2007; 293(6): F1761 - F1765. [Abstract] [Full Text] [PDF]

				O. Pochynyuk, J. D. Stockand, and A. Staruschenko Ion Channel Regulation by Ras, Rho, and Rab Small GTPases Experimental Biology and Medicine, November 1, 2007; 232(10): 1258 - 1265. [Abstract] [Full Text] [PDF]

				O. Pochynyuk, Q. Tong, J. Medina, A. Vandewalle, A. Staruschenko, V. Bugaj, and J. D. Stockand Molecular Determinants of PI(4,5)P2 and PI(3,4,5)P3 Regulation of the Epithelial Na+ Channel J. Gen. Physiol., September 24, 2007; 130(4): 399 - 413. [Abstract] [Full Text] [PDF]

				A. Staruschenko, O. Pochynyuk, A. Vandewalle, V. Bugaj, and J. D. Stockand Acute Regulation of the Epithelial Na+ Channel by Phosphatidylinositide 3-OH Kinase Signaling in Native Collecting Duct Principal Cells J. Am. Soc. Nephrol., June 1, 2007; 18(6): 1652 - 1661. [Abstract] [Full Text] [PDF]

				O. Pochynyuk, A. Staruschenko, V. Bugaj, L. LaGrange, and J. D. Stockand Quantifying RhoA Facilitated Trafficking of the Epithelial Na+ Channel toward the Plasma Membrane with Total Internal Reflection Fluorescence-Fluorescence Recovery after Photobleaching J. Biol. Chem., May 11, 2007; 282(19): 14576 - 14585. [Abstract] [Full Text] [PDF]