Rescue of functional ΔF508‐CFTR channels by co‐expression with truncated CFTR constructs in COS‐1 cells

FEBS Letters

Owsianik, Grzegorz¹  Cao, Lishuang¹  Nilius, Bernd¹ 

[1] Laboratory of Physiology, Catholic University of Leuven, Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium

关键词: Cystic fibrosis;    Cystic fibrosis transmembrane conductance regulator;    ΔF508-CFTR mutant;    Channel activity;    Co-expression;    Electrophysiology;    CFTR;    cystic fibrosis transmembrane conductance regulator;    ER;    endoplasmic reticulum;    NBD;    nucleotide binding domain;    GFP;    green fluorescent protein;    PCR;    polymerase chain reaction;    aa;    amino acid;   

DOI  :  10.1016/S0014-5793(03)01162-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The most frequent mutant variant of the cystic fibrosis transmembrane conductance regulator (CFTR), ΔF508-CFTR, is misprocessed and subsequently degraded in the endoplasmic reticulum. Using the patch-clamp technique, we showed that co-expressions of ΔF508-CFTR with the N-terminal CFTR truncates containing bi-arginine (RXR) retention/retrieval motifs result in a functional rescue of the ΔF508-CFTR mutant channel in COS-1 cells. This ΔF508-CFTR rescue process was strongly impaired when truncated CFTR constructs possessed either the ΔF508 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 ΔF508-CFTR channels.

【 授权许可】

Unknown