Association of cystic fibrosis transmembrane conductance regulator with epithelial sodium channel subunits carrying Liddle's syndrome mutations

被引:2
作者
Rooj, Arun K. [1 ]
Cormet-Boyaka, Estelle [2 ]
Clark, Edlira B. [1 ]
Qadri, Yawar J. [3 ]
Lee, William [4 ]
Boddu, Ravindra [5 ]
Agarwal, Anupam [5 ]
Tambi, Richa [6 ]
Uddin, Mohammed [6 ]
Parpura, Vladimir [4 ]
Sorscher, Eric J. [7 ]
Fuller, Cathy M. [1 ]
Berdiev, Bakhrom K. [1 ,6 ]
机构
[1] Univ Alabama Birmingham, Sch Med, Dept Cell Dev & Integrat Biol, Birmingham, AL 35294 USA
[2] Ohio State Univ, Dept Vet Biosci, Columbus, OH 43210 USA
[3] Emory Univ, Sch Med, Dept Anesthesiol, Atlanta, GA 30322 USA
[4] Univ Alabama Birmingham, Dept Neurobiol, Sch Med, Birmingham, AL USA
[5] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL USA
[6] Mohammed Bin Rashid Univ Med & Hlth Sci, Coll Med, Dubai, U Arab Emirates
[7] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA
基金
美国国家卫生研究院;
关键词
CFTR; cystic fibrosis; ENaC; FLIM; Liddle's syndrome; GREEN FLUORESCENT PROTEIN; UBIQUITIN LIGASE NEDD4L; CELL-SURFACE EXPRESSION; NA+ CHANNEL; BETA-SUBUNIT; FUNCTIONAL INTERACTIONS; MISSENSE MUTATION; MOLECULAR PROXIMITY; CHLORIDE CHANNELS; OPEN PROBABILITY;
D O I
10.1152/ajplung.00298.2020
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The association of the cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC) in the pathophysiology of cystic fibrosis (CF) is controversial. Previously, we demonstrated a close physical association between wild-type (WT) CFTR and WT ENaC. We have also shown that the F508del CFTR fails to associate with ENaC unless the mutant protein is rescued pharmacologically or by low temperature. In this study, we present the evidence for a direct physical association between WT CFTR and ENaC subunits carrying Liddle's syndrome mutations. We show that all three ENaC subunits bearing Liddle's syndrome mutations (both point mutations and the complete truncation of the carboxy terminus), could be coimmunoprecipitated with WT CFTR. The biochemical studies were complemented by fluorescence lifetime imaging microscopy (FLIM), a distance-dependent approach that monitors protein-protein interactions between fluorescently labeled molecules. Our measurements revealed significantly increased fluorescence resonance energy transfer between CFTR and all tested ENaC combinations as compared with controls (ECFP and EYFP cotransfected cells). Our findings are consistent with the notion that CFTR and ENaC are within reach of each other even in the setting of Liddle's syndrome mutations, suggestive of a direct intermolecular interaction between these two proteins.
引用
收藏
页码:L308 / L320
页数:13
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