A selective ER‐phagy exerts procollagen quality control via a Calnexin‐FAM134B complex

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
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.
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Metadaten
Author:Alison Forrester, Chiara De Leonibus, Paolo Grumati, Elisa Fasana, Marilina Piemontese, Leopoldo Staiano, Ilaria Fregno, Andrea Raimondi, Alessandro Marazza, Gemma Bruno, Maria Iavazzo, Daniela Intartaglia, Marta Seczynska, Eelco van Anken, Ivan Conte, Maria Antonietta De Matteis, Ivan Dikic, Maurizio Molinari, Carmine Settembre
URN:urn:nbn:de:hebis:30:3-525500
DOI:http://dx.doi.org/10.15252/embj.201899847
ISSN:1460-2075
ISSN:0261-4189
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=30559329
Parent Title (English):The EMBO journal
Publisher:EMBO Press ; Wiley
Place of publication:Heidelberg ; Hoboken, NJ [u. a.]
Document Type:Article
Language:English
Year of Completion:2018
Date of first Publication:2018/12/17
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/02/19
Tag:Calnexin; FAM134B; autophagy; collagen; endoplasmic reticulum
Volume:38
Issue:2, e99847
Pagenumber:16
First Page:1
Last Page:16
Note:
© 2018 The Authors. Published under the terms of the CC BY 4.0 license
HeBIS PPN:46142648X
Institutes:Medizin
Exzellenzcluster Makromolekulare Komplexe
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0

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