Rescue of functional DeltaF508-CFTR channels by co-expression with truncated CFTR constructs in COS-1 cells.
The most frequent mutant variant of the cystic fibrosis transmembrane conductance regulator (CFTR), DeltaF508-CFTR, is misprocessed and subsequently degraded in the endoplasmic reticulum. Using the patch-clamp technique, we showed that co-expressions of DeltaF508-CFTR with the N-terminal CFTR truncates containing bi-arginine (RXR) retention/retrieval motifs result in a functional rescue of the DeltaF508-CFTR mutant channel in COS-1 cells. This DeltaF508-CFTR rescue process was strongly impaired when truncated CFTR constructs possessed either the DeltaF508 mutation or arginine-to-lysine mutations in RXRs. In conclusions, our data demonstrated that expression of truncated CFTR constructs could be a novel promising approach to improve maturation of DeltaF508-CFTR channels.
Owsianik
Grzegorz
G
Laboratory of Physiology, Catholic University of Leuven, Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. grzegorz.owsianik@med.kuleuven.ac.be
Cao
Lishuang
L
Nilius
Bernd
B
D000818:Animals; D019556:COS Cells; D002712:Chlorides / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000502:physiology; D004594:Electrophysiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D009154:Mutation; D018408:Patch-Clamp Techniques; D015202:Protein Engineering; D014162:Transfection
D002712:Chlorides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP