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The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Rag GTPases mediate amino acid–dependent recruitment of TFEB and MITF to lysosomes

Martina, Jose A., Puertollano, Rosa·2013·Journal of Cell Biology
DOI 10.1083/jcb.201209135PMC PMC3575543
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Abstract

The mTORC1 complex supports cell growth and proliferation in response to energy levels, growth factors, and nutrients. The Rag guanosine triphosphatases (GTPases) activate mTORC1 in response to amino acids by promoting its redistribution to lysosomes. In this paper, we identify a novel role for Rags in controlling activation of transcription factor EB (TFEB), a master regulator of autophagic and lysosomal gene expression. Interaction of TFEB with active Rag heterodimers promoted recruitment of TFEB to lysosomes, leading to mTORC1-dependent phosphorylation and inhibition of TFEB. The interaction of TFEB with Rags required the first 30 residues of TFEB and the switch regions of the Rags G domain. Depletion or inactivation of Rags prevented recruitment of TFEB to lysosomes, whereas expression of active Rags induced association of TFEB with lysosomal membranes. Finally, Rag GTPases bound and regulated activation of microphthalmia-associated transcription factor, suggesting a broader role for Rags in the control of gene expression. Our work provides new insight into the molecular mechanisms that link nutrient availability and TFEB localization and activation.

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  • The FLCN/FNIP complex is a critical regulator of TFEB and TFE3 activation; by promoting GDP-loading of RAGC, FLCN facilitates interaction of TFEB/TFE3 with RAGs, resulting in their retention in the cytosol.

    “The Folliculin (FLCN)/Folliculin-interacting protein (FNIP) complex is a critical regulator of TFEB and TFE3 activation. By promoting GDP-loading of RAGC27, FLCN facilitates interaction of TFEB/TFE3 with RAGs, resulting in retention of the transcription factors in the cytosol28,29.”

    From TMEM55B links autophagy flux, lysosomal repair, and TFE3 activation in response to oxidative stress (2024) · cites this paper as [28]

    The Results section (“TFEB interacts with active Rags,” page unavailable) shows that TFEB binds active Rag heterodimers containing GDP-bound RagC, and the Introduction says this binding enables phosphorylation and cytosolic retention. Our copy does not establish that FLCN/FNIP promotes RagC GDP-loading or facilitates that interaction, and it studies MITF rather than TFE3. (LLM, conf=0.86)

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Citations

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Research works printed but not linked: 25

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  17. Sancak, 2008, The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1, Science., 320, 1496, 10.1126/science.1157535 · DOI · Paper page
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Metadata

Authors
Martina, J. A., & Puertollano, R.
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2013-02-11
Volume
200
Issue
4
Pages
475-491
ISSN
  • 1540-8140
  • 0021-9525
DOI
10.1083/jcb.201209135
PMC
PMC3575543
Cited by
354
References
6
Language
en

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