Cytoskeletal vimentin regulates cell size and autophagy through mTORC1 signaling

Ponnuswamy Mohanasundaram, Leila S Coelho-Rato, Mayank Kumar Modi, Marta Urbanska, Franziska Lautenschläger, Fang Cheng, John E Eriksson

Research output: Contribution to journalArticleScientificpeer-review

10 Citations (Scopus)
38 Downloads (Pure)

Abstract

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.

Original languageEnglish
Article numbere3001737
Number of pages21
JournalPLoS Biology
Volume20
Issue number9
DOIs
Publication statusPublished - 13 Sept 2022
MoE publication typeA1 Journal article-refereed

Keywords

  • Animals
  • Autophagy/physiology
  • Cell Size
  • GTP Phosphohydrolases/metabolism
  • Intermediate Filaments/metabolism
  • Mechanistic Target of Rapamycin Complex 1/metabolism
  • Mice
  • Multiprotein Complexes/metabolism
  • Signal Transduction
  • Vimentin/metabolism

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