ArticlePLoS biology2022
Folliculin promotes substrate-selective mTORC1 activity by activating RagC to recruit TFE3.
Article in PLoS biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 40 citations in OpenAlex.
- Synergistic role of TFEB/TFE3 and mTORC1 in kidney cystogenesis and tumorigenesis.Cell death and differentiation · 2026Article
- AMPK promotes TFEB transcriptional activity through dephosphorylation at both MTORC1-dependent and -independent sites.Autophagy · 2026Article
- Maspardin/SPG21 controls lysosome motility and TFEB phosphorylation through RAB7 positioning.The Journal of cell biology · 2026Article
- Differential contribution of TFE3 isoforms to cell motility and invasion.EMBO reports · 2026Article
- FLCN loss is characterized by SQSTM1/p62 accumulation despite functional autophagy flux in Birt-Hogg-Dubé syndrome-associated kidney cancer.Autophagy reports · 2026Article
- Substrate-selective mTORC1 regulation and gene dosage-dependent tissue divergence in Birt-Hogg-Dubé syndrome.Frontiers in oncology · 2026Review
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Gal3-CaN-Smurf1 Complex Sequestrates FLCN-FNIPs to Facilitate TFEB Activation in Response to Endomembrane Damage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- New developments in AMPK and mTORC1 cross-talk.Essays in biochemistry · 2024Review
- Rag-Ragulator is the central organizer of the physical architecture of the mTORC1 nutrient-sensing pathway.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Ragopathies and the rising influence of RagGTPases on human diseases.Nature communications · 2024Review
- Characterizing the tumor suppressor activity of FLCN in Birt-Hogg-Dubé syndrome through transcriptiomic and proteomic analysis.Research square · 2024Article
- TFEB drives mTORC1 hyperactivation and kidney disease in Tuberous Sclerosis Complex.Nature communications · 2024Article
- The molecular basis of nutrient sensing and signalling by mTORC1 in metabolism regulation and disease.Nature reviews. Molecular cell biology · 2023Review
- Lysosomes in senescence and aging.EMBO reports · 2023Review
- TFEB and TFE3 control glucose homeostasis by regulating insulin gene expression.The EMBO journal · 2023Article
- Article
- Induction of lysosomal exocytosis and biogenesis via TRPML1 activation for the treatment of uranium-induced nephrotoxicity.Nature communications · 2023Article
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Mechanistic target of rapamycin complex I (mTORC1) is central to cellular metabolic regulation. mTORC1 phosphorylates a myriad of substrates, but how different substrate specificity is conferred on mTORC1 by different conditions remains poorly defined. Here, we show how loss of the mTORC1 regulator folliculin (FLCN) renders mTORC1 specifically incompetent to phosphorylate TFE3, a master regulator of lysosome biogenesis, without affecting phosphorylation of other canonical mTORC1 substrates, such as S6 kinase. FLCN is a GTPase-activating protein (GAP) for RagC, a component of the mTORC1 amino acid (AA) sensing pathway, and we show that active RagC is necessary and sufficient to recruit TFE3 onto the lysosomal surface, allowing subsequent phosphorylation of TFE3 by mTORC1. Active mutants of RagC, but not of RagA, rescue both phosphorylation and lysosomal recruitment of TFE3 in the absence of FLCN. These data thus advance the paradigm that mTORC1 substrate specificity is in part conferred by direct recruitment of substrates to the subcellular compartments where mTORC1 resides and identify potential targets for specific modulation of specific branches of the mTOR pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.