Next Article in Journal
Nanoparticle-Based Delivery of Tumor Suppressor microRNA for Cancer Therapy
Next Article in Special Issue
Mechanisms of Disulfide Bond Formation in Nascent Polypeptides Entering the Secretory Pathway
Previous Article in Journal
Microfluidic Device for On-Chip Immunophenotyping and Cytogenetic Analysis of Rare Biological Cells
Open AccessArticle

Protein Translocation Acquires Substrate Selectivity Through ER Stress-Induced Reassembly of Translocon Auxiliary Components

1
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 05505, Korea
2
Asian Medical Institute of Convergence Science and Technology, Asan Medical Center, Seoul 05505, Korea
3
Department of Convergence Medicine, Asian Medical Center, Seoul 05505, Korea
*
Author to whom correspondence should be addressed.
Cells 2020, 9(2), 518; https://doi.org/10.3390/cells9020518
Received: 6 February 2020 / Revised: 20 February 2020 / Accepted: 24 February 2020 / Published: 24 February 2020
(This article belongs to the Special Issue Redox-dependent ER processes)
Protein import across the endoplasmic reticulum membrane is physiologically regulated in a substrate-selective manner to ensure the protection of stressed ER from the overload of misfolded proteins. However, it is poorly understood how different types of substrates are accurately distinguished and disqualified during translocational regulation. In this study, we found poorly assembled translocon-associated protein (TRAP) complexes in stressed ER. Immunoaffinity purification identified calnexin in the TRAP complex in which poor assembly inhibited membrane insertion of the prion protein (PrP) in a transmembrane sequence-selective manner, through translocational regulation. This reaction was induced selectively by redox perturbation, rather than calcium depletion, in the ER. The liberation of ERp57 from calnexin appeared to be the reason for the redox sensitivity. Stress-independent disruption of the TRAP complex prevented a pathogenic transmembrane form of PrP (ctmPrP) from accumulating in the ER. This study uncovered a previously unappreciated role for calnexin in assisting the redox-sensitive function of the TRAP complex and provided insights into the ER stress-induced reassembly of translocon auxiliary components as a key mechanism by which protein translocation acquires substrate selectivity. View Full-Text
Keywords: protein translocation; protein quality control; prion protein; ER stress; redox homeostasis protein translocation; protein quality control; prion protein; ER stress; redox homeostasis
Show Figures

Graphical abstract

MDPI and ACS Style

Lee, S.; Shin, Y.; Kim, K.; Song, Y.; Kim, Y.; Kang, S.-W. Protein Translocation Acquires Substrate Selectivity Through ER Stress-Induced Reassembly of Translocon Auxiliary Components. Cells 2020, 9, 518.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop