TY  - JOUR
A1  - Reggio, Alessio
A1  - Buonomo, Viviana
A1  - Berkane, Rayene
A1  - Bhaskara, Ramachandra M.
A1  - Tellechea, Mariana
A1  - Peluso, Ivana
A1  - Polishchuk, Elena
A1  - Di Lorenzo, Giorgia
A1  - Cirillo, Carmine
A1  - Esposito, Marianna
A1  - Hussain, Adeela
A1  - Hübner, Antje-Kathrin
A1  - Hübner, Christian
A1  - Settembre, Carmine
A1  - Hummer, Gerhard
A1  - Grumati, Paolo
A1  - Stolz, Alexandra
T1  - Role of FAM134 paralogues in endoplasmic reticulum remodeling, ER-phagy, and Collagen quality control
T2  - EMBO reports
N2  - 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.
KW  - autophagy
KW  - Collagen
KW  - ER stress
KW  - ER-phagy
KW  - FAM134
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63934
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-639345
SN  - 1469-3178
N1  - 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.
N1  - Open Access funding enabled and organized by Projekt DEAL.
N1  - 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).
VL  - 22
IS  - 9, art. e52289
SP  - 1
EP  - 20
PB  - Wiley; EMBO Press
CY  - Heidelberg; Hoboken, NJ [u.a.]
ER  -