MicroRNA 802 stimulates ROMK channels by suppressing caveolin-1

Dao Hong Lin, Peng Yue, Chunyang Pan, Peng Sun, Wen Hui Wang

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

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 highpotassium 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.

Original languageEnglish
Pages (from-to)1087-1098
Number of pages12
JournalJournal of the American Society of Nephrology : JASN
Volume22
Issue number6
DOIs
StatePublished - Jun 2011
Externally publishedYes

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