Regulation of ENaC biogenesis by the stress response protein SERP1

Diana Faria, Nicolas Lentze, Joana Almaca, Simão Luz, Luisa Alessio, Yuemin Tian, José Paulo Martins, Pedro Cruz, Rainer Schreiber, Mandana Rezwan, Carlos Miguel Farinha, Daniel Auerbach, Margarida D. Amaral, Karl Kunzelmann

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Cystic fibrosis lung disease is caused by reduced Cl - secretion along with enhanced Na + absorption, leading to reduced airway surface liquid and compromised mucociliary clearance. Therapeutic strategies have been developed to activate cystic fibrosis transmembrane conductance regulator (CFTR) or to overcome enhanced Na + absorption by the epithelial Na + channel (ENaC). In a split-ubiquitin-based two-hybrid screening, we identified stress-associated ER protein 1 (SERP1)/ribosome-associated membrane protein 4 as a novel interacting partner for the ENaC β-subunit. SERP1 is induced during cell stress and interacts with the molecular chaperone calnexin, thus controlling early biogenesis of membrane proteins. ENaC activity was measured in the human airway epithelial cell lines H441 and A549 and in voltage clamp experiments with ENaC-overexpressing Xenopus oocytes. We found that expression of SERP1 strongly inhibits amiloride-sensitive Na + transport. SERP1 coimmunoprecipitated and colocalized with βENaC in the endoplasmic reticulum, together with the chaperone calnexin. In contrast to the inhibitory effects on ENaC, SERP1 appears to promote expression of CFTR. Taken together, SERP1 is a novel cochaperone and regulator of ENaC expression.

Original languageEnglish (US)
Pages (from-to)819-827
Number of pages9
JournalPflugers Archiv European Journal of Physiology
Volume463
Issue number6
DOIs
StatePublished - Jun 1 2012
Externally publishedYes

Fingerprint

Epithelial Sodium Channels
Heat-Shock Proteins
Calnexin
Proteins
Cystic Fibrosis Transmembrane Conductance Regulator
Membrane Proteins
Bridge clearances
Mucociliary Clearance
Pulmonary diseases
Molecular Chaperones
Amiloride
Clamping devices
Ubiquitin
Xenopus
Ribosomes
Cystic Fibrosis
Endoplasmic Reticulum
Lung Diseases
Oocytes
Screening

Keywords

  • Calnexin
  • CFTR
  • Cystic fibrosis transmembrane conductance regulator
  • ENaC
  • RAMP4
  • SERP1

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

Cite this

Regulation of ENaC biogenesis by the stress response protein SERP1. / Faria, Diana; Lentze, Nicolas; Almaca, Joana; Luz, Simão; Alessio, Luisa; Tian, Yuemin; Martins, José Paulo; Cruz, Pedro; Schreiber, Rainer; Rezwan, Mandana; Farinha, Carlos Miguel; Auerbach, Daniel; Amaral, Margarida D.; Kunzelmann, Karl.

In: Pflugers Archiv European Journal of Physiology, Vol. 463, No. 6, 01.06.2012, p. 819-827.

Research output: Contribution to journalArticle

Faria, D, Lentze, N, Almaca, J, Luz, S, Alessio, L, Tian, Y, Martins, JP, Cruz, P, Schreiber, R, Rezwan, M, Farinha, CM, Auerbach, D, Amaral, MD & Kunzelmann, K 2012, 'Regulation of ENaC biogenesis by the stress response protein SERP1', Pflugers Archiv European Journal of Physiology, vol. 463, no. 6, pp. 819-827. https://doi.org/10.1007/s00424-012-1091-1
Faria, Diana ; Lentze, Nicolas ; Almaca, Joana ; Luz, Simão ; Alessio, Luisa ; Tian, Yuemin ; Martins, José Paulo ; Cruz, Pedro ; Schreiber, Rainer ; Rezwan, Mandana ; Farinha, Carlos Miguel ; Auerbach, Daniel ; Amaral, Margarida D. ; Kunzelmann, Karl. / Regulation of ENaC biogenesis by the stress response protein SERP1. In: Pflugers Archiv European Journal of Physiology. 2012 ; Vol. 463, No. 6. pp. 819-827.
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