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Class III PI-3-kinase activates phospholipase D in an amino acid–sensing mTORC1 pathway

The rapamycin-sensitive mammalian target of rapamycin (mTOR) complex, mTORC1, regulates cell growth in response to mitogenic signals and amino acid availability. Phospholipase D (PLD) and its product, phosphatidic acid, have been established as mediators of mitogenic activation of mTORC1. In this st...

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Autores principales: Yoon, Mee-Sup, Du, Guangwei, Backer, Jonathan M., Frohman, Michael A., Chen, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206351/
https://www.ncbi.nlm.nih.gov/pubmed/22024166
http://dx.doi.org/10.1083/jcb.201107033
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author Yoon, Mee-Sup
Du, Guangwei
Backer, Jonathan M.
Frohman, Michael A.
Chen, Jie
author_facet Yoon, Mee-Sup
Du, Guangwei
Backer, Jonathan M.
Frohman, Michael A.
Chen, Jie
author_sort Yoon, Mee-Sup
collection PubMed
description The rapamycin-sensitive mammalian target of rapamycin (mTOR) complex, mTORC1, regulates cell growth in response to mitogenic signals and amino acid availability. Phospholipase D (PLD) and its product, phosphatidic acid, have been established as mediators of mitogenic activation of mTORC1. In this study, we identify a novel role for PLD1 in an amino acid–sensing pathway. We find that amino acids activate PLD1 and that PLD1 is indispensable for amino acid activation of mTORC1. Activation of PLD1 by amino acids requires the class III phosphatidylinositol 3-kinase hVps34, which stimulates PLD1 activity through a functional interaction between phosphatidylinositol 3-phosphate and the Phox homology (PX) domain of PLD1. Furthermore, amino acids stimulate PLD1 translocation to the lysosomal region where mTORC1 activation occurs in an hVps34-dependent manner, and this translocation is necessary for mTORC1 activation. The PX domain is required for PLD1 translocation, mTORC1 activation, and cell size regulation. Finally, we show that the hVps34-PLD1 pathway acts independently of, and in parallel to, the Rag pathway in regulating amino acid activation of mTORC1.
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spelling pubmed-32063512012-04-30 Class III PI-3-kinase activates phospholipase D in an amino acid–sensing mTORC1 pathway Yoon, Mee-Sup Du, Guangwei Backer, Jonathan M. Frohman, Michael A. Chen, Jie J Cell Biol Research Articles The rapamycin-sensitive mammalian target of rapamycin (mTOR) complex, mTORC1, regulates cell growth in response to mitogenic signals and amino acid availability. Phospholipase D (PLD) and its product, phosphatidic acid, have been established as mediators of mitogenic activation of mTORC1. In this study, we identify a novel role for PLD1 in an amino acid–sensing pathway. We find that amino acids activate PLD1 and that PLD1 is indispensable for amino acid activation of mTORC1. Activation of PLD1 by amino acids requires the class III phosphatidylinositol 3-kinase hVps34, which stimulates PLD1 activity through a functional interaction between phosphatidylinositol 3-phosphate and the Phox homology (PX) domain of PLD1. Furthermore, amino acids stimulate PLD1 translocation to the lysosomal region where mTORC1 activation occurs in an hVps34-dependent manner, and this translocation is necessary for mTORC1 activation. The PX domain is required for PLD1 translocation, mTORC1 activation, and cell size regulation. Finally, we show that the hVps34-PLD1 pathway acts independently of, and in parallel to, the Rag pathway in regulating amino acid activation of mTORC1. The Rockefeller University Press 2011-10-31 /pmc/articles/PMC3206351/ /pubmed/22024166 http://dx.doi.org/10.1083/jcb.201107033 Text en © 2011 Yoon et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Yoon, Mee-Sup
Du, Guangwei
Backer, Jonathan M.
Frohman, Michael A.
Chen, Jie
Class III PI-3-kinase activates phospholipase D in an amino acid–sensing mTORC1 pathway
title Class III PI-3-kinase activates phospholipase D in an amino acid–sensing mTORC1 pathway
title_full Class III PI-3-kinase activates phospholipase D in an amino acid–sensing mTORC1 pathway
title_fullStr Class III PI-3-kinase activates phospholipase D in an amino acid–sensing mTORC1 pathway
title_full_unstemmed Class III PI-3-kinase activates phospholipase D in an amino acid–sensing mTORC1 pathway
title_short Class III PI-3-kinase activates phospholipase D in an amino acid–sensing mTORC1 pathway
title_sort class iii pi-3-kinase activates phospholipase d in an amino acid–sensing mtorc1 pathway
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206351/
https://www.ncbi.nlm.nih.gov/pubmed/22024166
http://dx.doi.org/10.1083/jcb.201107033
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