Recent Progress in CFTR Interactome Mapping and Its Importance for Cystic Fibrosis.

Sang Hyun Lim,Jamie Snider,Elizabeth-Ann Legere,Igor Stagljar

doi:10.3389/fphar.2017.00997

Abstract

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a chloride channel found in secretory epithelia with a plethora of known interacting proteins. Mutations in the CFTR gene cause cystic fibrosis (CF), a disease that leads to progressive respiratory illness and other complications of phenotypic variance resulting from perturbations of this protein interaction network. Studying the collection of CFTR interacting proteins and the differences between the interactomes of mutant and wild type CFTR provides insight into the molecular machinery of the disease and highlights possible therapeutic targets. This mini review focuses on functional genomics and proteomics approaches used for systematic, high-throughput identification of CFTR-interacting proteins to provide comprehensive insight into CFTR regulation and function.

Highlights

Cystic Fibrosis (CF) is a life-shortening genetic disease that affects multiple organs including the lungs, pancreas, liver, intestines, and the reproductive tract
The CFTR protein, regulated by phosphorylation and nucleotide binding, functions as an anion channel that mediates the flux of chloride and bicarbonate ions (Riordan, 2008), Abbreviations: APIP, APAF1 Interacting Protein; CF, Cystic Fibrosis; CFTR, Cystic Fibrosis Transmembrane Conductance Regulator; EHF, ETS Homologous Factor; Protein-protein interactions (PPIs), Protein-Protein Interactions; singlenucleotide polymorphism (SNP), Single-Nucleotide Polymorphism
Three Hsp90 co-chaperones were found to be involved in regulating channel folding and/or export from the ER, and by using RNA-interference (RNAi) knockdown, Aha1 was discovered to inhibit coupling of F508del CFTR to the ER export machinery (Wang et al, 2006)

Summary

Introduction

Cystic Fibrosis (CF) is a life-shortening genetic disease that affects multiple organs including the lungs, pancreas, liver, intestines, and the reproductive tract. There has been a growing interest in CFTR proteomics over the last decade, with analysis of CFTRinteracting proteins becoming an important means of understanding the cell-specific environments associated with wild type and mutant CFTR, and their corresponding functional consequences (Wang and Li, 2001; Li and Naren, 2005; Collawn et al, 2010).

Results

Conclusion