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Synergistic activation of ENaC by three membrane-bound channel-activating serine proteases (mCAP1, mCAP2, and mCAP3) and serum- and glucocorticoid-regulated kinase (Sgk1) in Xenopus oocytes
- Source :
- Journal of General Physiology. August, 2002, Vol. 120 Issue 2, p191, 11 p.
- Publication Year :
- 2002
-
Abstract
- Sodium balance is maintained by the precise regulation of the activity of the epithelial sodium channel (ENaC) in the kidney. We have recently reported an extracellular activation of ENaC-mediated sodium transport ([I.sub.Na]) by a GPI-anchored serine protease (mouse channel-activating protein, mCAP1) that was isolated from a cortical collecting duct cell line derived from mouse kidney. In the present study, we have identified two additional membrane-bound serine proteases (mCAP2 and mCAP3) that are expressed in the same cell line. We show that each of these proteases is able to increase [I.sub.Na] 6-10-fold in the Xenopus oocyte expression system. [I.sub.Na] and the number (N) of channels expressed at the cell surface (measured by binding of a FLAG monoclonal [I.sup.125]-radioiodinated antibody) were measured in the same oocyte. Using this assay, we show that mCAP1 increases [I.sub.Na] 10-fold (P < 0.001) but N remained unchanged (P = 0.9), indicating that mCAP1 regulates ENaC activity by increasing its average open probability of the whole cell (wc[P.sub.o]). The serum- and glucocorticoid-regulated kinase (Sgk1) involved in the aldosterone-dependent signaling cascade enhances [I.sub.Na] by 2.5-fold (P < 0.001) and N by 1.6-fold (P < 0.001), indicating a dual effect on N and wc[P.sub.o]. Compared with Sgk1 alone, coexpression of Sgk1 with mCAP1 leads to a ninefold increase in [I.sub.Na] (P < 0.001) and 1.3-fold in N (P < 0.02). Similar results were observed for mCAP2 and mCAP3. The synergism between CAPs and Sgk1 on [I.sub.Na] was always more than additive, indicating a true potentiation. The synergistic effect of the two activation pathways allows a large dynamic range for ENaC-mediated sodium regulation crucial for a tight control of sodium homeostasis. KEY WORDS: epithelial sodium channel * amiloride * serum glucocorticoid-regulated kinase 1 (Sgk1) * aldosterone * NEDD4
Details
- ISSN :
- 00221295
- Volume :
- 120
- Issue :
- 2
- Database :
- Gale General OneFile
- Journal :
- Journal of General Physiology
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.90990856