Ragulator Is a GEF for the Rag GTPases that Signal Amino Acid Levels to mTORC1
The mTOR Complex 1 (mTORC1) pathway regulates cell growth in response to numerous cues, including amino acids, which promote mTORC1 translocation to the lysosomal surface, its site of activation. The heterodimeric RagA/B-RagC/D GTPases, the Ragulator complex that tethers the Rags to the lysosome, an...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/85631 https://orcid.org/0000-0002-1446-7256 https://orcid.org/0000-0001-9765-4016 |
| _version_ | 1811083751696891904 |
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| author | Bar-Peled, Liron Zoncu, Roberto Sabatini, David M. Schweitzer, Lawrence David Sabatini, David |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Bar-Peled, Liron Zoncu, Roberto Sabatini, David M. Schweitzer, Lawrence David Sabatini, David |
| author_sort | Bar-Peled, Liron |
| collection | MIT |
| description | The mTOR Complex 1 (mTORC1) pathway regulates cell growth in response to numerous cues, including amino acids, which promote mTORC1 translocation to the lysosomal surface, its site of activation. The heterodimeric RagA/B-RagC/D GTPases, the Ragulator complex that tethers the Rags to the lysosome, and the v-ATPase form a signaling system that is necessary for amino acid sensing by mTORC1. Amino acids stimulate the binding of guanosine triphosphate to RagA and RagB but the factors that regulate Rag nucleotide loading are unknown. Here, we identify HBXIP and C7orf59 as two additional Ragulator components that are required for mTORC1 activation by amino acids. The expanded Ragulator has nucleotide exchange activity toward RagA and RagB and interacts with the Rag heterodimers in an amino acid- and v-ATPase-dependent fashion. Thus, we provide mechanistic insight into how mTORC1 senses amino acids by identifying Ragulator as a guanine nucleotide exchange factor (GEF) for the Rag GTPases. |
| first_indexed | 2024-09-23T12:38:29Z |
| format | Article |
| id | mit-1721.1/85631 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:38:29Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/856312022-10-01T10:12:09Z Ragulator Is a GEF for the Rag GTPases that Signal Amino Acid Levels to mTORC1 Bar-Peled, Liron Zoncu, Roberto Sabatini, David M. Schweitzer, Lawrence David Sabatini, David Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Koch Institute for Integrative Cancer Research at MIT Bar-Peled, Liron Schweitzer, Lawrence David Sabatini, David M. The mTOR Complex 1 (mTORC1) pathway regulates cell growth in response to numerous cues, including amino acids, which promote mTORC1 translocation to the lysosomal surface, its site of activation. The heterodimeric RagA/B-RagC/D GTPases, the Ragulator complex that tethers the Rags to the lysosome, and the v-ATPase form a signaling system that is necessary for amino acid sensing by mTORC1. Amino acids stimulate the binding of guanosine triphosphate to RagA and RagB but the factors that regulate Rag nucleotide loading are unknown. Here, we identify HBXIP and C7orf59 as two additional Ragulator components that are required for mTORC1 activation by amino acids. The expanded Ragulator has nucleotide exchange activity toward RagA and RagB and interacts with the Rag heterodimers in an amino acid- and v-ATPase-dependent fashion. Thus, we provide mechanistic insight into how mTORC1 senses amino acids by identifying Ragulator as a guanine nucleotide exchange factor (GEF) for the Rag GTPases. National Institutes of Health (U.S.) (Grant CA103866) National Institutes of Health (U.S.) (Grant AI47389) United States. Dept. of Defense (Grant W81XWH-07-0448) LAM Foundation National Cancer Institute (U.S.) (Fellowship F31CA167872) 2014-03-14T16:57:27Z 2014-03-14T16:57:27Z 2012-09 2012-06 Article http://purl.org/eprint/type/JournalArticle 00928674 1097-4172 http://hdl.handle.net/1721.1/85631 Bar-Peled, Liron et al. “Ragulator Is a GEF for the Rag GTPases That Signal Amino Acid Levels to mTORC1.” Cell 150.6 (2012): 1196–1208. Copyright © 2012 Elsevier Inc. https://orcid.org/0000-0002-1446-7256 https://orcid.org/0000-0001-9765-4016 en_US http://dx.doi.org/10.1016/j.cell.2012.07.032 Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier Open Archive |
| spellingShingle | Bar-Peled, Liron Zoncu, Roberto Sabatini, David M. Schweitzer, Lawrence David Sabatini, David Ragulator Is a GEF for the Rag GTPases that Signal Amino Acid Levels to mTORC1 |
| title | Ragulator Is a GEF for the Rag GTPases that Signal Amino Acid Levels to mTORC1 |
| title_full | Ragulator Is a GEF for the Rag GTPases that Signal Amino Acid Levels to mTORC1 |
| title_fullStr | Ragulator Is a GEF for the Rag GTPases that Signal Amino Acid Levels to mTORC1 |
| title_full_unstemmed | Ragulator Is a GEF for the Rag GTPases that Signal Amino Acid Levels to mTORC1 |
| title_short | Ragulator Is a GEF for the Rag GTPases that Signal Amino Acid Levels to mTORC1 |
| title_sort | ragulator is a gef for the rag gtpases that signal amino acid levels to mtorc1 |
| url | http://hdl.handle.net/1721.1/85631 https://orcid.org/0000-0002-1446-7256 https://orcid.org/0000-0001-9765-4016 |
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