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 Đikić, Maurizio Molinari, Carmine Settembre
- 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.
MetadatenAuthor: | Alison Forrester, Chiara De Leonibus, Paolo GrumatiORCiDGND, 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 ĐikićORCiDGND, Maurizio Molinari, Carmine Settembre |
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URN: | urn:nbn:de:hebis:30:3-525500 |
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DOI: | https://doi.org/10.15252/embj.201899847 |
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ISSN: | 1460-2075 |
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ISSN: | 0261-4189 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/30559329 |
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Parent Title (English): | The EMBO journal |
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Publisher: | EMBO Press ; Wiley |
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Place of publication: | Heidelberg ; Hoboken, NJ [u. a.] |
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Document Type: | Article |
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Language: | English |
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Year of Completion: | 2018 |
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Date of first Publication: | 2018/12/17 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2020/02/19 |
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Tag: | Calnexin; FAM134B; autophagy; collagen; endoplasmic reticulum |
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Volume: | 38 |
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Issue: | 2, e99847 |
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Page Number: | 16 |
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First Page: | 1 |
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Last Page: | 16 |
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Note: | © 2018 The Authors. Published under the terms of the CC BY 4.0 license |
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HeBIS-PPN: | 46142648X |
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Institutes: | Medizin / Medizin |
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| Exzellenzcluster / Exzellenzcluster Makromolekulare Komplexe |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 4.0 |
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