Phosphorylation site independent single R‐domain mutations affect CFTR channel activity

FEBS Letters

Wei, Lin¹  Cuppens, Harry²  Cassiman, Jean-Jacques²  Nilius, Bernd¹  Droogmans, Guy¹  Vankeerberghen, Anne² 

[1] Department of Physiology, Campus Gasthuisberg, KU Leuven, Herestraat 49, B-3000 Louvain, Belgium;Centre for Human Genetics, Campus Gasthuisberg, KU Leuven, B-3000 Louvain, Belgium

关键词: Cystic fibrosis transmembrane conductance regulator;    R-domain mutation;    Xenopus oocyte;    COS cell;    Green fluorescent protein;   

DOI  :  10.1016/S0014-5793(98)01351-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We investigated CFTR channel activity of mature R-domain mutants showing single alterations at sites other than the predicted phosphorylation sites. All mutations were found in cystic fibrosis (CF) patients (H620Q, E822K and E826K). The macroscopic CFTR chloride conductance induced by phosphorylation was significantly enhanced in Xenopus oocytes injected with mRNA of H620Q but reduced in the E822K and E826K mutants compared to wild type CFTR. The anion permeability sequence for all three mutants was the same as that of wild type CFTR. Cell attached single channel studies in COS cells revealed that both open channel probability and/or the number of functional channels were either higher (H620Q) or lower (E822K and E826K) than in wild type CFTR. Single channel conductances were unchanged in all mutants. Our results suggest that additional sites in the R-domain other than phosphorylation sites influence gating of CFTR channels.

【 授权许可】

Unknown