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Macropinocytosis drives T cell growth by sustaining the activation of mTORC1
Macropinocytosis is an evolutionarily-conserved, large-scale, fluid-phase form of endocytosis that has been ascribed different functions including antigen presentation in macrophages and dendritic cells, regulation of receptor density in neurons, and regulation of tumor growth under nutrient-limitin...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954116/ https://www.ncbi.nlm.nih.gov/pubmed/31924779 http://dx.doi.org/10.1038/s41467-019-13997-3 |
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author | Charpentier, John C. Chen, Di Lapinski, Philip E. Turner, Jackson Grigorova, Irina Swanson, Joel A. King, Philip D. |
author_facet | Charpentier, John C. Chen, Di Lapinski, Philip E. Turner, Jackson Grigorova, Irina Swanson, Joel A. King, Philip D. |
author_sort | Charpentier, John C. |
collection | PubMed |
description | Macropinocytosis is an evolutionarily-conserved, large-scale, fluid-phase form of endocytosis that has been ascribed different functions including antigen presentation in macrophages and dendritic cells, regulation of receptor density in neurons, and regulation of tumor growth under nutrient-limiting conditions. However, whether macropinocytosis regulates the expansion of non-transformed mammalian cells is unknown. Here we show that primary mouse and human T cells engage in macropinocytosis that increases in magnitude upon T cell activation to support T cell growth even under amino acid (AA) replete conditions. Mechanistically, macropinocytosis in T cells provides access of extracellular AA to an endolysosomal compartment to sustain activation of the mechanistic target of rapamycin complex 1 (mTORC1) that promotes T cell growth. Our results thus implicate a function of macropinocytosis in mammalian cell growth beyond Ras-transformed tumor cells via sustained mTORC1 activation. |
format | Online Article Text |
id | pubmed-6954116 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69541162020-01-13 Macropinocytosis drives T cell growth by sustaining the activation of mTORC1 Charpentier, John C. Chen, Di Lapinski, Philip E. Turner, Jackson Grigorova, Irina Swanson, Joel A. King, Philip D. Nat Commun Article Macropinocytosis is an evolutionarily-conserved, large-scale, fluid-phase form of endocytosis that has been ascribed different functions including antigen presentation in macrophages and dendritic cells, regulation of receptor density in neurons, and regulation of tumor growth under nutrient-limiting conditions. However, whether macropinocytosis regulates the expansion of non-transformed mammalian cells is unknown. Here we show that primary mouse and human T cells engage in macropinocytosis that increases in magnitude upon T cell activation to support T cell growth even under amino acid (AA) replete conditions. Mechanistically, macropinocytosis in T cells provides access of extracellular AA to an endolysosomal compartment to sustain activation of the mechanistic target of rapamycin complex 1 (mTORC1) that promotes T cell growth. Our results thus implicate a function of macropinocytosis in mammalian cell growth beyond Ras-transformed tumor cells via sustained mTORC1 activation. Nature Publishing Group UK 2020-01-10 /pmc/articles/PMC6954116/ /pubmed/31924779 http://dx.doi.org/10.1038/s41467-019-13997-3 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Charpentier, John C. Chen, Di Lapinski, Philip E. Turner, Jackson Grigorova, Irina Swanson, Joel A. King, Philip D. Macropinocytosis drives T cell growth by sustaining the activation of mTORC1 |
title | Macropinocytosis drives T cell growth by sustaining the activation of mTORC1 |
title_full | Macropinocytosis drives T cell growth by sustaining the activation of mTORC1 |
title_fullStr | Macropinocytosis drives T cell growth by sustaining the activation of mTORC1 |
title_full_unstemmed | Macropinocytosis drives T cell growth by sustaining the activation of mTORC1 |
title_short | Macropinocytosis drives T cell growth by sustaining the activation of mTORC1 |
title_sort | macropinocytosis drives t cell growth by sustaining the activation of mtorc1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954116/ https://www.ncbi.nlm.nih.gov/pubmed/31924779 http://dx.doi.org/10.1038/s41467-019-13997-3 |
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