Hsc70 negatively regulates epithelial sodium channel trafficking at multiple sites in epithelial cells

Rebecca A. Chanoux, Calla B. Shubin, Amal Robay, Laurence Suaud, Ronald C. Rubenstein

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The epithelial sodium channel (ENaC) plays an important role in homeostasis of blood pressure and of the airway surface liquid, and excess function of ENaC results in refractory hypertension (in Liddle's syndrome) and impaired mucociliary clearance (in cystic fibrosis). The regulation of ENaC by molecular chaperones, such as the 70-kDa heat shock protein Hsc70, is not completely understood. Our previously published data suggest that Hsc70 negatively affects ENaC activity and surface expression in Xenopus oocytes; here we investigate the mechanism by which Hsc70 acts on ENaC in epithelial cells. In Madin-Darby canine kidney cells stably expressing epitope-tagged αβγ-ENaC and with tetracycline-inducible overexpression of Hsc70, treatment with 5 μg/ml doxycycline increased total Hsc70 expression 20%. This increase in Hsc70 expression led to a decrease in ENaC activity and surface expression that corresponded to an increased rate of functional ENaC retrieval from the cell surface. In addition, Hsc70 overexpression decreased the association of newly synthesized ENaC subunits. These data support the hypothesis that Hsc70 inhibits ENaC functional expression at the apical surface of epithelia by regulating ENaC biogenesis and ENaC trafficking at the cell surface.

Original languageEnglish
JournalAmerican Journal of Physiology - Cell Physiology
Volume305
Issue number7
DOIs
Publication statusPublished - 1 Oct 2013
Externally publishedYes

Fingerprint

Epithelial Sodium Channels
Liddle Syndrome
Epithelial Cells
Mucociliary Clearance
Madin Darby Canine Kidney Cells
Molecular Chaperones
HSP70 Heat-Shock Proteins
Doxycycline
Xenopus
Tetracycline
Cystic Fibrosis
Oocytes
Epitopes
Homeostasis
Epithelium
Blood Pressure
Hypertension

Keywords

  • Chaperone
  • ENaC
  • Epithelia
  • Heat shock protein
  • Trafficking

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

Cite this

Hsc70 negatively regulates epithelial sodium channel trafficking at multiple sites in epithelial cells. / Chanoux, Rebecca A.; Shubin, Calla B.; Robay, Amal; Suaud, Laurence; Rubenstein, Ronald C.

In: American Journal of Physiology - Cell Physiology, Vol. 305, No. 7, 01.10.2013.

Research output: Contribution to journalArticle

Chanoux, Rebecca A. ; Shubin, Calla B. ; Robay, Amal ; Suaud, Laurence ; Rubenstein, Ronald C. / Hsc70 negatively regulates epithelial sodium channel trafficking at multiple sites in epithelial cells. In: American Journal of Physiology - Cell Physiology. 2013 ; Vol. 305, No. 7.
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