Forrester, Alison; De Leonibus, Chiara; Grumati, Paolo; Fasana, Elisa; Piemontese, Marilina; Staiano, Leopoldo; Fregno, Ilaria; Raimondi, Andrea; Marazza, Alessandro; Bruno, Gemma; Iavazzo, Maria; Intartaglia, Daniela; Seczynska, Marta; van Anken, Eelco; Conte, Ivan; De Matteis, Maria Antonietta; Dikic, Ivan; Molinari, Maurizio; Settembre, Carmine (2019). A selective ER-phagy exerts procollagen quality control via a Calnexin-FAM134B complex. The EMBO journal, 38(2) EMBO Press 10.15252/embj.201899847
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Autophagy is a cytosolic quality control process that recognizes substrates through receptor-mediated mechanisms. Procollagens, the most abundant gene products in Metazoa, are synthesized in the endoplasmic reticulum (ER), and a fraction that fails to attain the native structure is cleared by autophagy. However, how autophagy selectively recognizes misfolded procollagens in the ER lumen is still unknown. We performed siRNA interference, CRISPR-Cas9 or knockout-mediated gene deletion of candidate autophagy and ER proteins in collagen producing cells. We found that the ER-resident lectin chaperone Calnexin (CANX) and the ER-phagy receptor FAM134B are required for autophagy-mediated quality control of endogenous procollagens. Mechanistically, CANX acts as co-receptor that recognizes ER luminal misfolded procollagens and interacts with the ER-phagy receptor FAM134B. In turn, FAM134B binds the autophagosome membrane-associated protein LC3 and delivers a portion of ER containing both CANX and procollagen to the lysosome for degradation. Thus, a crosstalk between the ER quality control machinery and the autophagy pathway selectively disposes of proteasome-resistant misfolded clients from the ER.
Item Type: |
Journal Article (Original Article) |
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Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
Subjects: |
500 Science 500 Science > 570 Life sciences; biology |
ISSN: |
1460-2075 |
Publisher: |
EMBO Press |
Language: |
English |
Submitter: |
Edith Desideria Imthurn |
Date Deposited: |
28 Jun 2019 18:18 |
Last Modified: |
28 Nov 2020 02:29 |
Publisher DOI: |
10.15252/embj.201899847 |
PubMed ID: |
30559329 |
Uncontrolled Keywords: |
Calnexin FAM134B autophagy collagen endoplasmic reticulum |
BORIS DOI: |
10.7892/boris.130257 |
URI: |
https://boris.unibe.ch/id/eprint/130257 |
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