Cytoskeletal vimentin regulates cell size and autophagy through mTORC1 signaling

The nutrient-activated mTORC1 (mechanistic target of rapamycin kinase complex 1) signaling pathway determines cell size by controlling mRNA translation, ribosome biogenesis, protein synthesis, and autophagy. Here, we show that vimentin, a cytoskeletal intermediate filament protein that we have known...

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Bibliographic Details
Published in:PLoS biology 2022-09, Vol.20 (9), p.e3001737-e3001737
Main Authors: Mohanasundaram, Ponnuswamy, Coelho-Rato, Leila S, Modi, Mayank Kumar, Urbanska, Marta, Lautenschläger, Franziska, Cheng, Fang, Eriksson, John E
Format: Article
Language:English
Subjects:
Adipocytes
Amino acids
Autophagy
Autophagy (Cytology)
Biological control systems
Biology and Life Sciences
Cell adhesion & migration
Cell cycle
Cell death
Cell growth
Cell size
Cellular proteins
Cellular signal transduction
Chemoreception
Cytoskeleton
Fibroblasts
Growth factors
Insulin
Keratin
Kinases
Medicine and Health Sciences
mRNA
Nutrients
Physical Sciences
Physiological aspects
Physiological research
Protein biosynthesis
Protein synthesis
Proteins
Rapamycin
Research and Analysis Methods
Signal transduction
Signaling
TOR protein
Translocation
Vimentin
Wound healing
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Summary:The nutrient-activated mTORC1 (mechanistic target of rapamycin kinase complex 1) signaling pathway determines cell size by controlling mRNA translation, ribosome biogenesis, protein synthesis, and autophagy. Here, we show that vimentin, a cytoskeletal intermediate filament protein that we have known to be important for wound healing and cancer progression, determines cell size through mTORC1 signaling, an effect that is also manifested at the organism level in mice. This vimentin-mediated regulation is manifested at all levels of mTOR downstream target activation and protein synthesis. We found that vimentin maintains normal cell size by supporting mTORC1 translocation and activation by regulating the activity of amino acid sensing Rag GTPase. We also show that vimentin inhibits the autophagic flux in the absence of growth factors and/or critical nutrients, demonstrating growth factor-independent inhibition of autophagy at the level of mTORC1. Our findings establish that vimentin couples cell size and autophagy through modulating Rag GTPase activity of the mTORC1 signaling pathway.
ISSN:1545-7885
1544-9173
1545-7885
DOI:10.1371/journal.pbio.3001737