BIBLIOS

Document type
Journal articles

Document subtype
Full paper

Title
CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput screening system

Participants in the publication
Sang Hyun Lim (Author)
Jamie Snider (Author)
Liron Birimberg-Schwartz (Author)
Wan Ip (Author)
Joana C Serralha (Author)
BioISI - Biosystems & Integrative Sciences Institute
Hugo M Botelho (Author)
Dep. Química e Bioquímica
BioISI
Miquéias Lopes-Pacheco (Author)
Dep. Química e Bioquímica
BioISI
Madalena C Pinto (Author)
BioISI
Mohamed Taha Moutaoufik (Author)
Mara Zilocchi (Author)
Onofrio Laselva (Author)
Mohsen Esmaeili (Author)
Max Kotlyar (Author)
Anna Lyakisheva (Author)
Priscilla Tang (Author)
Lucía López Vázquez (Author)
Indira Akula (Author)
Farzaneh Aboualizadeh (Author)
Victoria Wong (Author)
Ingrid Grozavu (Author)
Teuta Opacak-Bernardi (Author)
Zhong Yao (Author)
Meg Mendoza (Author)
Mohan Babu (Author)
Igor Jurisica (Author)
Tanja Gonska (Author)
Christine E Bear (Author)
Margarida D Amaral (Author)
Dep. Química e Bioquímica
BioISI
Igor Stagljar (Author)

Summary
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a chloride and bicarbonate channel in secretory epithelia with a critical role in maintaining fluid homeostasis. Mutations in CFTR are associated with Cystic Fibrosis (CF), the most common lethal autosomal recessive disorder in Caucasians. While remarkable treatment advances have been made recently in the form of modulator drugs directly rescuing CFTR dysfunction, there is still considerable scope for improvement of therapeutic effectiveness. Here, we report the application of a high-throughput screening variant of the Mammalian Membrane Two-Hybrid (MaMTH-HTS) to map the protein-protein interactions of wild-type (wt) and mutant CFTR (F508del), in an effort to better understand CF cellular effects and identify new drug targets for patient-specific treatments. Combined with functional validation in multiple disease models, we have uncovered candidate proteins with potential roles in CFTR function/CF pathophysiology, including Fibrinogen Like 2 (FGL2), which we demonstrate in patient-derived intestinal organoids has a significant effect on CFTR functional expression.


Where published
Molecular Systems Biology

Publication Identifiers
ISSN - 1744-4292

Publisher
EMBO


Document Identifiers
DOI - https://doi.org/10.15252/msb.202110629
URL - http://dx.doi.org/10.15252/msb.202110629

Rankings
Web Of Science Q1 (2020) - 11.429 - BIOCHEMISTRY & MOLECULAR BIOLOGY - SCIE
SCIMAGO Q1 (2020) - 8.523 - Biochemistry, Genetics and Molecular Biology (miscellaneous)
SCIMAGO Q1 (2020) - 8.523 - Computational Theory and Mathematics
SCIMAGO Q1 (2020) - 8.523 - Information Systems
SCIMAGO Q1 (2020) - 8.523 - Medicine (miscellaneous)
SCOPUS Q1 (2020) - 15.6 - Applied Mathematics
SCOPUS Q1 (2020) - 15.6 - Biochemistry, Genetics and Molecular Biology (all)
SCIMAGO Q1 (2019) - 7.338 - Applied Mathematics
SCIMAGO Q1 (2019) - 7.338 - Biochemistry, Genetics and Molecular Biology (miscellaneous)
SCIMAGO Q1 (2019) - 7.338 - Computational Theory and Mathematics

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