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

Autori
Lim, SH ; Snider, J ; Birimberg-Schwartz, L ; Ip, W ; Serralha, JC ; Botelho, HM ; Lopes-Pacheco, M ; Pinto, MC ; Moutaoufik, MT ; Zilocchi, M ; Laselva, O ; Esmaeili, M ; Kotlyar, M ; Lyakisheva, A ; Tang, P ; Lopez Vazquez, L ; Akula, I ; Aboualizadeh, F ; Wong, V ; Grozavu, I ; Opacak-Bernardi, T ; Yao, Z ; Mendoza, M ; Babu, M ; Jurisica, I ; Gonska, T ; Bear, CE ; Amara, MD ; Stagljar, I

Izvornik
Molecular systems biology (1744-4292) 18 (2022); 10629, 23

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
cystic fibrosis ; high-throughput screening ; integrative computational biology ; interactome ; mammalian membrane two-hybrid

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA