title: MicroRNA 802 stimulates ROMK channels by suppressing caveolin-1.
abstract: Dietary potassium stimulates the surface expression of ROMK channels in the aldosterone-sensitive distal nephron, but the mechanism by which this occurs is incompletely understood. Here, a high-potassium diet increased the transcription of microRNA (miR) 802 in the cortical collecting duct in mice. In addition, high-potassium intake decreased the expression of caveolin-1, whose 3' untranslated region contains the seed sequence of miR-802. In vitro, expression of miR-802 suppressed the expression of caveolin-1, and conversely, downregulation of endogenous miR-802 increased the expression of caveolin-1. Sucrose-gradient centrifugation suggested that caveolin-1 closely associated with ROMK channels, and immunoprecipitation showed that caveolin-1 interacted with the N terminus of ROMK. Expression of caveolin-1 varied inversely with the expression of ROMK1 in the plasma membrane, and caveolin-1 inhibited ROMK1 channel activity. Removal of the clathrin-dependent endocytosis motif from ROMK1 failed to abolish the effect of caveolin-1 on ROMK1 channel activity. Last, expression of miR-802 increased ROMK1 channel activity, an effect blocked by coexpression of caveolin-1. Taken together, miR-802 mediates the stimulatory effect of a high-potassium diet on ROMK channel activity by suppressing caveolin-1 expression, which leads to increased surface expression of ROMK channels in the distal nephron.
authors.affiliation: Department of Pharmacology, New York Medical College, BSB 538, Valhalla, NY 10595, USA. daohong_lin@nymc.edu
authors.forename: Dao-Hong
authors.initials: DH
authors.lastname: Lin
authors.forename: Peng
authors.initials: P
authors.lastname: Yue
authors.forename: Chunyang
authors.initials: C
authors.lastname: Pan
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Wang
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism*; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D023421:Models, Animal; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D017419:Potassium, Dietary / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
chemical_list: D051242:Caveolin 1; C510693:Kcnj1 protein, mouse; C560526:MIRN802 microRNA, mouse; D035683:MicroRNAs; D024661:Potassium Channels, Inwardly Rectifying; D017419:Potassium, Dietary