Gαq activation modulates autophagy by promoting mTORC1 signaling.
Animals
Autophagy
CHO Cells
Cricetulus
Fibroblasts
/ cytology
GTP-Binding Protein alpha Subunits, Gq-G11
/ metabolism
HEK293 Cells
Humans
Lysosomes
/ metabolism
Male
Mechanistic Target of Rapamycin Complex 1
/ metabolism
Mice
Models, Biological
Phenotype
Protein Binding
Protein Domains
Rats, Wistar
Regulatory-Associated Protein of mTOR
/ metabolism
Sequestosome-1 Protein
/ metabolism
Signal Transduction
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
27 07 2021
27 07 2021
Historique:
received:
11
05
2020
accepted:
28
06
2021
entrez:
28
7
2021
pubmed:
29
7
2021
medline:
5
8
2021
Statut:
epublish
Résumé
The mTORC1 node plays a major role in autophagy modulation. We report a role of the ubiquitous Gαq subunit, a known transducer of plasma membrane G protein-coupled receptors signaling, as a core modulator of mTORC1 and autophagy. Cells lacking Gαq/11 display higher basal autophagy, enhanced autophagy induction upon different types of nutrient stress along with a decreased mTORC1 activation status. They are also unable to reactivate mTORC1 and thus inactivate ongoing autophagy upon nutrient recovery. Conversely, stimulation of Gαq/11 promotes sustained mTORC1 pathway activation and reversion of autophagy promoted by serum or amino acids removal. Gαq is present in autophagic compartments and lysosomes and is part of the mTORC1 multi-molecular complex, contributing to its assembly and activation via its nutrient status-sensitive interaction with p62, which displays features of a Gαq effector. Gαq emerges as a central regulator of the autophagy machinery required to maintain cellular homeostasis upon nutrient fluctuations.
Identifiants
pubmed: 34315875
doi: 10.1038/s41467-021-24811-4
pii: 10.1038/s41467-021-24811-4
pmc: PMC8316552
doi:
Substances chimiques
Regulatory-Associated Protein of mTOR
0
Rptor protein, mouse
0
Sequestosome-1 Protein
0
Sqstm1 protein, mouse
0
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
GTP-Binding Protein alpha Subunits, Gq-G11
EC 3.6.5.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4540Subventions
Organisme : NIA NIH HHS
ID : P01 AG031782
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG038072
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG021904
Pays : United States
Organisme : NIA NIH HHS
ID : R37 AG021904
Pays : United States
Informations de copyright
© 2021. The Author(s).
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