Improved maturation of CFTR by an ER export signal

Wendeler, M. W. and Nufer, O. and Hauri, H. -P.. (2007) Improved maturation of CFTR by an ER export signal. The FASEB Journal, Vol. 21, H. 10. pp. 2352-2358.

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Official URL: http://edoc.unibas.ch/dok/A5257741

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The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated chloride channel in the plasma membrane of several epithelial cells. Maturation of CFTR is inefficient in most cells, with only a fraction of nascent chains being properly folded and transported to the cell surface. The most common mutation in CFTR, CFTR-deltaF508, leads to the genetic disease cystic fibrosis. CFTR-deltaF508 has a temperature-sensitive folding defect and is almost quantitatively degraded in the endoplasmic reticulum (ER). Here we tested whether a strong ER export signal appended to CFTR improves its transport and surface expression. We show that a single valine ER export signal at the C terminus of the cytoplasmic tail of CFTR improves maturation of wild-type CFTR by 2-fold. This conservative mutation interfered with neither plasma membrane localization nor stability of mature CFTR. In contrast, the valine signal was unable to rescue CFTR-deltaF508 from ER-associated degradation. Our finding of improved maturation of CFTR mediated by a valine signal may be of potential use in gene therapy of cystic fibrosis. Moreover, failure of the valine signal to rescue CFTR-deltaF508 from ER degradation indicates that the inability of CFTR-deltaF508 to leave the ER is unlikely to be due to a malfunctioning ER export signal.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Pharmacology/Neurobiology (Hauri)
UniBasel Contributors:Hauri, Hans-Peter
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:22 Mar 2012 14:22
Deposited On:22 Mar 2012 13:29

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