BIBLIOS

Document type
Journal articles

Document subtype
Full paper

Title
Folding Status Is Determinant over Traffic-Competence in Defining CFTR Interactors in the Endoplasmic Reticulum

Participants in the publication
João D. Santos (Author)
BioISI - Biosystems & Integrative Sciences Institute
Sara Canato (Author)
BioISI - Biosystems & Integrative Sciences Institute
Ana S. Carvalho (Author)
Hugo M. Botelho (Author)
Dep. Química e Bioquímica
BioISI
Kerman Aloria (Author)
Margarida D. Amaral (Author)
Dep. Química e Bioquímica
BioISI
Rune Matthiesen (Author)
Andre O. Falcao (Author)
Dep. Informática
LASIGE
Carlos M. Farinha (Author)
Dep. Química e Bioquímica
BioISI

Summary
The most common cystic fibrosis-causing mutation (F508del, present in ~85% of CF patients) leads to CFTR misfolding, which is recognized by the endoplasmic reticulum (ER) quality control (ERQC), resulting in ER retention and early degradation. It is known that CFTR exit from the ER is mediated by specific retention/sorting signals that include four arginine-framed tripeptide (AFT) retention motifs and a diacidic (DAD) exit code that controls the interaction with the COPII machinery. Here, we aim at obtaining a global view of the protein interactors that regulate CFTR exit from the ER. We used mass spectrometry-based interaction proteomics and bioinformatics analyses to identify and characterize proteins interacting with selected CFTR peptide motifs or full-length CFTR variants retained or bypassing these ERQC checkpoints. We conclude that these ERQC trafficking checkpoints rely on fundamental players in the secretory pathway, detecting key components of the protein folding machinery associated with the AFT recognition and of the trafficking machinery recognizing the diacidic code. Furthermore, a greater similarity in terms of interacting proteins is observed for variants sharing the same folding defect over those reaching the same cellular location, evidencing that folding status is dominant over ER escape in shaping the CFTR interactome.


Institution
BioISI - Biosystems & Integrative Sciences Institute

Where published
Cells

Publication Identifiers
ISSN - 2073-4409

Publisher
MDPI AG



Document Identifiers
URL - http://dx.doi.org/10.3390/cells8040353
DOI - https://doi.org/10.3390/cells8040353

Rankings
SCIMAGO Q1 (2020) - 1.22 - Medicine (miscellaneous)
SCOPUS Q1 (2017) - 2.742 - General Biochemistry, Genetics and Molecular Biology
SCIMAGO Q1 (2020) - 1.22 - Medicine (miscellaneous)

Keywords
diacidic code arginine-framed tripeptides endoplasmic reticulum quality control CFTR interactome folding trafficking