An epithelial serine protease activates the amiloride-sensitive sodium channel
Détails
ID Serval
serval:BIB_B897F8027BAE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
An epithelial serine protease activates the amiloride-sensitive sodium channel
Périodique
Nature
ISSN
0028-0836 (Print)
Statut éditorial
Publié
Date de publication
10/1997
Volume
389
Numéro
6651
Pages
607-10
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Oct 9
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Oct 9
Résumé
Sodium balance, and ultimately blood pressure and extracellular fluid volume, is maintained by precise regulation of the activity of the epithelial sodium channel (ENaC). In a Xenopus kidney epithelial cell line (A6), exposure of the apical membrane to the protease inhibitor aprotinin reduces transepithelial sodium transport. Sodium-channel activity can be restored by subsequent exposure to the nonspecific protease trypsin. Using A6 cells and a functional complementation assay to detect increases in ENaC activity, we have cloned a 329-residue protein belonging to the serine protease family. We show that coexpression of this protein with ENaC in Xenopus oocytes increases the activity of the sodium channel by two- to threefold. This channel-activating protease (CAP1) is expressed in kidney, gut, lung, skin and ovary. Sequence analysis predicts that CAP1 is a secreted and/or glycosylphosphatidylinositol-anchored protein: ENaC activity would thus be regulated by the activity of a protease expressed at the surface of the same cell. This previously undiscovered mechanism for autocrine regulation may apply to other ion channels, in particular to members of the ENaC family that are present in neurons and epithelial cells.
Mots-clé
Amino Acid Sequence
Animals
Aprotinin/pharmacology
Cell Line
Cloning, Molecular
Epithelial Sodium Channel
Genetic Complementation Test
Humans
Ion Channel Gating
Molecular Sequence Data
Oocytes
RNA, Messenger/metabolism
Rats
Sequence Homology, Amino Acid
Serine Endopeptidases/genetics/*metabolism
Serine Proteinase Inhibitors/pharmacology
Sodium/metabolism
Sodium Channels/drug effects/genetics/*metabolism
Trypsin/pharmacology
Xenopus
*Xenopus Proteins
Pubmed
Web of science
Création de la notice
24/01/2008 13:38
Dernière modification de la notice
20/08/2019 16:26