Faria, Diana and Lentze, Nicolas and Almaca, Joana and Luz, Simao and Alessio, Luisa and Tian, Yuemin and Martins, Jose Paulo and Cruz, Pedro and Schreiber, Rainer and Rezwan, Mandana and Farinha, Carlos Miguel and Auerbach, Daniel and Amaral, Margarida D. and Kunzelmann, Karl (2012) Regulation of ENaC biogenesis by the stress response protein SERP1. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 463 (6). pp. 819-827. ISSN 0031-6768, 1432-2013
Full text not available from this repository. (Request a copy)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 beta-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 oocytes. We found that expression of SERP1 strongly inhibits amiloride-sensitive Na+ transport. SERP1 coimmunoprecipitated and colocalized with beta ENaC 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANSMEMBRANE CONDUCTANCE REGULATOR; ALVEOLAR EPITHELIAL-CELLS; ENDOPLASMIC-RETICULUM; MEMBRANE-PROTEINS; SODIUM-TRANSPORT; A549 CELLS; NA+; HYPOXIA; LUNG; CFTR; ENaC; SERP1; CFTR; Cystic fibrosis transmembrane conductance regulator; CFTR; RAMP4; Calnexin |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 May 2020 07:04 |
| Last Modified: | 13 May 2020 07:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18692 |
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