| mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase. | |
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MedLine Citation:
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PMID: 22053050 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The mTOR complex 1 (mTORC1) protein kinase is a master growth regulator that is stimulated by amino acids. Amino acids activate the Rag guanosine triphosphatases (GTPases), which promote the translocation of mTORC1 to the lysosomal surface, the site of mTORC1 activation. We found that the vacuolar H(+)-adenosine triphosphatase ATPase (v-ATPase) is necessary for amino acids to activate mTORC1. The v-ATPase engages in extensive amino acid-sensitive interactions with the Ragulator, a scaffolding complex that anchors the Rag GTPases to the lysosome. In a cell-free system, ATP hydrolysis by the v-ATPase was necessary for amino acids to regulate the v-ATPase-Ragulator interaction and promote mTORC1 translocation. Results obtained in vitro and in human cells suggest that amino acid signaling begins within the lysosomal lumen. These results identify the v-ATPase as a component of the mTOR pathway and delineate a lysosome-associated machinery for amino acid sensing. |
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Authors:
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Roberto Zoncu; Liron Bar-Peled; Alejo Efeyan; Shuyu Wang; Yasemin Sancak; David M Sabatini |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Science (New York, N.Y.) Volume: 334 ISSN: 1095-9203 ISO Abbreviation: Science Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-04 Completed Date: 2012-01-25 Revised Date: 2012-04-11 |
Medline Journal Info:
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Nlm Unique ID: 0404511 Medline TA: Science Country: United States |
Other Details:
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Languages: eng Pagination: 678-83 Citation Subset: IM |
Affiliation:
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Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acids
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metabolism* Animals Cell Line Drosophila GTP Phosphohydrolases / metabolism Humans Lysosomes / metabolism* Proteins / metabolism* RNA Interference Signal Transduction Vacuolar Proton-Translocating ATPases / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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AI47389/AI/NIAID NIH HHS; CA103866/CA/NCI NIH HHS; R01 CA103866-07/CA/NCI NIH HHS; R01 CA103866-08/CA/NCI NIH HHS; R01 CA103866-09/CA/NCI NIH HHS; R37 AI047389-11/AI/NIAID NIH HHS; R37 AI047389-12/AI/NIAID NIH HHS; R37 AI047389-13/AI/NIAID NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids; 0/Proteins; 0/mTORC1 complex, human; EC 3.6.1.-/GTP Phosphohydrolases; EC 3.6.1.-/Vacuolar Proton-Translocating ATPases |
| Comments/Corrections | |
Comment In:
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Science. 2011 Nov 4;334(6056):611-2
[PMID:
22053037
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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