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 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Renal Physiology
Volume305
Issue number1
DOIs
StatePublished - Jul 1 2013

Fingerprint

Zyxin
Hepatocyte Nuclear Factor 1
Epithelial Cells
Kidney
Epidermal Growth Factor
Transcription Factors
LIM Domain Proteins
RNA Interference
Immunoprecipitation
Small Interfering RNA
Intestines
Cell Movement
Cysts
Pancreas

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Zyxin regulates migration of renal epithelial cells through activation of hepatocyte nuclear factor-1β. / Choi, Yun Hee; McNally, Brian T.; Igarashi, Peter.

In: American Journal of Physiology - Renal Physiology, Vol. 305, No. 1, 01.07.2013.

Research output: Contribution to journalArticle

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