Role of FAM134 paralogues in endoplasmic reticulum remodeling, ER-phagy, and Collagen quality control.
Collagen
ER stress
ER-phagy
FAM134
autophagy
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
06 09 2021
06 09 2021
Historique:
revised:
07
07
2021
received:
16
12
2020
accepted:
08
07
2021
pubmed:
3
8
2021
medline:
25
2
2023
entrez:
2
8
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34338405
doi: 10.15252/embr.202052289
pmc: PMC8447607
doi:
Substances chimiques
Membrane Proteins
0
Collagen
9007-34-5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e52289Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
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