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

Détails

Ressource 1Télécharger: BIB_097890CD65E0.P001.pdf (1936.02 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_097890CD65E0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
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
Périodique
Journal of General Physiology
Auteur(s)
Vuagniaux G., Vallet V., Jaeger N. F., Hummler E., Rossier B. C.
ISSN
0022-1295
Statut éditorial
Publié
Date de publication
08/2002
Peer-reviewed
Oui
Volume
120
Numéro
2
Pages
191-201
Notes
Journal Article Research Support, Non-U.S. Gov't --- Old month value: Aug
Résumé
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(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(Na) 6-10-fold in the Xenopus oocyte expression system. I(Na) and the number (N) of channels expressed at the cell surface (measured by binding of a FLAG monoclonal I(125)-radioiodinated antibody) were measured in the same oocyte. Using this assay, we show that mCAP1 increases I(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 (wcP(o)). The serum- and glucocorticoid-regulated kinase (Sgk1) involved in the aldosterone-dependent signaling cascade enhances I(Na) by 2.5-fold (P < 0.001) and N by 1.6-fold (P < 0.001), indicating a dual effect on N and wcP(o). Compared with Sgk1 alone, coexpression of Sgk1 with mCAP1 leads to a ninefold increase in I(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(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.
Mots-clé
Animals Cell Line/chemistry Drug Interactions Drug Synergism Epithelial Sodium Channel Immediate-Early Proteins Membrane Proteins/isolation & purification/pharmacology/*physiology Mice *Nuclear Proteins Oocytes Protein-Serine-Threonine Kinases/pharmacology/*physiology Rats Serine Endopeptidases/isolation & purification/pharmacology/*physiology *Serpins Sodium Channels/drug effects/*metabolism Xenopus
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 14:00
Dernière modification de la notice
20/08/2019 13:31
Données d'usage