Zyxin regulates migration of renal epithelial cells through activation of hepatocyte nuclear factor-1β

Yun Hee Choi, Brian T. McNally, Peter Igarashi

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Hepatocyte nuclear factor-1β (HNF-1β) is an epithelial tissue-specific transcription factor that regulates gene expression in the kidney, liver, pancreas, intestine, and other organs. Mutations of HNF-1β in humans produce renal cysts and congenital kidney anomalies. Here, we identify the LIM-domain protein zyxin as a novel binding partner of HNF-1β in renal epithelial cells. Zyxin shuttles to the nucleus where it colocalizes with HNF-1β. Immunoprecipitation of zyxin in leptomycin B-treated cells results in coprecipitation of HNF-1β. The protein interaction requires the second LIM domain of zyxin and two distinct domains of HNF-1β. Overexpression of zyxin stimulates the transcriptional activity of HNF-1β, whereas small interfering RNA silencing of zyxin inhibits HNF-1β-dependent transcription. Epidermal growth factor (EGF) induces translocation of zyxin into the nucleus and stimulates HNF-1β-dependent promoter activity. The EGF-mediated nuclear translocation of zyxin requires activation of Akt. Expression of dominant-negative mutant HNF-1β, knockdown of zyxin, or inhibition of Akt inhibits EGF-stimulated cell migration. These findings reveal a novel pathway by which extracellular signals are transmitted to the nucleus to regulate the activity of a transcription factor that is essential for renal epithelial differentiation.

Original languageEnglish (US)
Pages (from-to)F100-F110
JournalAmerican Journal of Physiology - Renal Physiology
Volume305
Issue number1
DOIs
StatePublished - Jul 1 2013

Keywords

  • Cell motility
  • Epidermal growth factor
  • Protein-protein interactions
  • Transcription

ASJC Scopus subject areas

  • Physiology
  • Urology

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