Role of FAM134 paralogues in endoplasmic reticulum remodeling, ER-phagy, and Collagen quality control

  • Degradation of the endoplasmic reticulum (ER) via selective autophagy (ER-phagy) is vital for cellular homeostasis. We identify FAM134A/RETREG2 and FAM134C/RETREG3 as ER-phagy receptors, which predominantly exist in an inactive state under basal conditions. Upon autophagy induction and ER stress signal, they can induce significant ER fragmentation and subsequent lysosomal degradation. FAM134A, FAM134B/RETREG1, and FAM134C are essential for maintaining ER morphology in a LC3-interacting region (LIR)-dependent manner. Overexpression of any FAM134 paralogue has the capacity to significantly augment the general ER-phagy flux upon starvation or ER-stress. Global proteomic analysis of FAM134 overexpressing and knockout cell lines reveals several protein clusters that are distinctly regulated by each of the FAM134 paralogues as well as a cluster of commonly regulated ER-resident proteins. Utilizing pro-Collagen I, as a shared ER-phagy substrate, we observe that FAM134A acts in a LIR-independent manner and compensates for the loss of FAM134B and FAM134C, respectively. FAM134C instead is unable to compensate for the loss of its paralogues. Taken together, our data show that FAM134 paralogues contribute to common and unique ER-phagy pathways.
Metadaten
Author:Alessio Reggio, Viviana Buonomo, Rayene Berkane, Ramachandra M. BhaskaraORCiD, Mariana TellecheaORCiD, Ivana Peluso, Elena Polishchuk, Giorgia Di Lorenzo, Carmine Cirillo, Marianna Esposito, Adeela Hussain, Antje-Kathrin Hübner, Christian Hübner, Carmine Settembre, Gerhard HummerORCiD, Paolo GrumatiORCiDGND, Alexandra StolzORCiDGND
URN:urn:nbn:de:hebis:30:3-639345
DOI:https://doi.org/10.15252/embr.202052289
ISSN:1469-3178
Parent Title (English):EMBO reports
Publisher:Wiley; EMBO Press
Place of publication:Heidelberg; Hoboken, NJ [u.a.]
Document Type:Article
Language:English
Date of Publication (online):2021/08/02
Date of first Publication:2021/08/02
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/04/05
Tag:Collagen; ER stress; ER-phagy; FAM134; autophagy
Volume:22
Issue:9, art. e52289
Page Number:20
First Page:1
Last Page:20
Note:
This work was supported by grants to PG: Telethon Foundation (TMPGCBX16TT), Roche Foundation (Roche per la Ricerca 2019), AFM-Telethon (Trampoline Grant 2020); and to AS: Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Project-ID 259130777—SFB 1177, the Else Kroener Fresenius Stiftung (2016_A196), and the EU/EFPIA/OICR/McGill/KTH/Diamond Innovative Medicines Initiative 2 Joint Undertaking (EUbOPEN grant n° 875510). AR is supported by Fondazione Umberto Veronesi. CAH was funded by the DFG (HU 800/6-2 and RTG 1715). RMB and GH thank the Max Planck Society for support.
Note:
Open Access funding enabled and organized by Projekt DEAL.
Note:
The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD021690 (http://www.ebi.ac.uk/pride/archive/projects/PXD021690) (MEFs proteomes) and PXD025626 (http://www.ebi.ac.uk/pride/archive/projects/PXD025626) (U2OS proteomes).
HeBIS-PPN:493481524
Institutes:Medizin
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0