Folliculin tunes mTORC1 toward TFE3

FLCN–RagC signaling makes mTORC1 substrate-selective for TFE3 phosphorylation under amino-acid cues.

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Folliculin promotes substrate-selective mTORC1 activity by activating RagC to recruit TFE3

Li K, Wada S, Gosis BS, et al. · PLoS biology · 2022

doi.org/10.1371/journal.pbio.3001594 Read the full paper ↗41 citationscc by

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Folliculin tunes mTORC1 toward TFE3

These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.

mTORC1.

Introduction The ability of a cell to sense and respond to the intracellular and extracellular environment is vital for it to maintain metabolic homeostasis.

TFE3 transcription factor.

Doing so is also fundamentally necessary for the cell to align its metabolic programming to ongoing cellular physiological needs.

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What they did

Manipulated amino acids, GATOR, FLCN, and RagC in C2C12 cells and read TFE3 phosphorylation/localization.

What they found

TFE3 phosphorylation depends strongly on amino acids; FLCN promotes RagC activity to recruit TFE3.

The limits

What it doesn't show

Mostly cell-culture mechanism; organismal physiology needs separate tests.

Key terms

mTORC1: Nutrient-sensing kinase complex.
Folliculin (FLCN): GAP regulator acting via RagC.
RagC: Rag GTPase aiding lysosomal recruitment.
TFE3: Transcription factor for lysosome biogenesis.
Amino-acid sensing: Nutrient input to mTORC1.
GATOR: Complex regulating Rag pathway.

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Common questions

Kinase?

mTORC1.

Adaptor focus?

FLCN/RagC.

Substrate?

TFE3.

Key cue?

Amino acids.