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Publication details

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)
Sara Canato (Author)
Ana S. Carvalho (Author)
Hugo M. Botelho (Author)
BIOISI - Instituto de Biossistemas e Ciências Integrativas
Kerman Aloria (Author)
Margarida D. Amaral (Author)
Dep. Química e Bioquímica
BIOISI - Instituto de Biossistemas e Ciências Integrativas
Rune Matthiesen (Author)
Andre O. Falcao (Author)
Dep. Informática
LASIGE - LASIGE
Carlos M. Farinha (Author)
Dep. Química e Bioquímica
BIOISI - Instituto de Biossistemas e Ciências Integrativas

Scope
International

Refereeing
Yes

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.

Date of Submisson/Request
2019-02-28
Date of Acceptance
2019-04-12
Date of Publication
2019-04-14

Institution
BioISI - Biosystems & Integrative Sciences Institute

Where published
Cells

Publication Identifiers
ISSN - 2073-4409

Publisher
MDPI AG

Volume
8
Number
4

Starting page
353

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

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


Export

APA
João D. Santos, Sara Canato, Ana S. Carvalho, Hugo M. Botelho, Kerman Aloria, Margarida D. Amaral, Rune Matthiesen, Andre O. Falcao, Carlos M. Farinha, (2019). Folding Status Is Determinant over Traffic-Competence in Defining CFTR Interactors in the Endoplasmic Reticulum. Cells, 8, ISSN 2073-4409. eISSN . http://dx.doi.org/10.3390/cells8040353

IEEE
João D. Santos, Sara Canato, Ana S. Carvalho, Hugo M. Botelho, Kerman Aloria, Margarida D. Amaral, Rune Matthiesen, Andre O. Falcao, Carlos M. Farinha, "Folding Status Is Determinant over Traffic-Competence in Defining CFTR Interactors in the Endoplasmic Reticulum" in Cells, vol. 8, 2019. 10.3390/cells8040353

BIBTEX
@article{39281, author = {João D. Santos and Sara Canato and Ana S. Carvalho and Hugo M. Botelho and Kerman Aloria and Margarida D. Amaral and Rune Matthiesen and Andre O. Falcao and Carlos M. Farinha}, title = {Folding Status Is Determinant over Traffic-Competence in Defining CFTR Interactors in the Endoplasmic Reticulum}, journal = {Cells}, year = 2019, volume = 8 }