Regulation of a sodium channel-associated G-protein by aldosterone.
The action of aldosterone to increase apical membrane permeability in responsive epithelia is thought to be due to activation of sodium channels. This channel is regulated, in part, by G-proteins, but it is not known if this mechanism is regulated by aldosterone. We report that aldosterone stimulates the expression of the 41-kDa alphai3 subunit of the heterotrimeric GTP-binding proteins in A-6 cells. Both mRNA and the total amount of this protein are increased by aldosterone. The G-protein is palmitoylated in response to the steroid, and the newly synthesized subunit is found to co-localize with the sodium channel. Aldosterone stimulation of sodium transport is significantly inhibited by inhibition of palmitoylation. These results suggest that aldosterone regulates sodium channel activity in epithelia through stimulation of the expression and post-translational targeting of a channel regulatory G-protein subunit.
Rokaw
M D
MD
Laboratory of Epithelial Cell Biology, Renal-Electrolyte Division, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Benos
D J
DJ
Palevsky
P M
PM
Cunningham
S A
SA
West
M E
ME
Johnson
J P
JP
D000450:Aldosterone / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D006706:Homeostasis; D007700:Kinetics; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism / Q000494:pharmacology; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000502:physiology*; D014982:Xenopus laevis
D000906:Antibodies; D046911:Macromolecular Substances; D010169:Palmitic Acids; D010455:Peptides; D015222:Sodium Channels; C040514:2-fluorohexadecanoic acid; D019308:Palmitic Acid; D000450:Aldosterone; D012964:Sodium; D019204:GTP-Binding Proteins