Macropinosomes as units of signal transduction.
Identifieur interne : 000288 ( Main/Exploration ); précédent : 000287; suivant : 000289Macropinosomes as units of signal transduction.
Auteurs : Joel A. Swanson [États-Unis] ; Sei Yoshida [États-Unis]Source :
- Philosophical transactions of the Royal Society of London. Series B, Biological sciences [ 1471-2970 ] ; 2019.
Descripteurs français
- KwdFr :
- MESH :
- physiologie : Endosomes, Pinocytose, Prolifération cellulaire, Transduction du signal.
- Animaux, Humains.
English descriptors
- KwdEn :
- MESH :
- physiology : Cell Proliferation, Endosomes, Pinocytosis, Signal Transduction.
- Animals, Humans.
Abstract
Macropinosome formation occurs as a localized sequence of biochemical activities and associated morphological changes, which may be considered a form of signal transduction leading to the construction of an organelle. Macropinocytosis may also convey information about the availability of extracellular nutrients to intracellular regulators of metabolism. Consistent with this idea, activation of the metabolic regulator mechanistic target of rapamycin complex-1 (mTORC1) in response to acute stimulation by growth factors and extracellular amino acids requires internalization of amino acids by macropinocytosis. This suggests that macropinocytosis is necessary for mTORC1-dependent growth of metazoan cells, both as a route for delivery of amino acids to sensors associated with lysosomes and as a platform for growth factor-dependent signalling to mTORC1 via phosphatidylinositol 3-kinase (PI3K) and the Akt pathway. Because the biochemical signals required for the construction of macropinosomes are also required for cell growth, and inhibition of macropinocytosis inhibits growth factor signalling to mTORC1, we propose that signalling by growth factor receptors is organized into stochastic, structure-dependent cascades of chemical reactions that both build a macropinosome and stimulate mTORC1. More generally, as discrete units of signal transduction, macropinosomes may be subject to feedback regulation by metabolism and cell dimensions. This article is part of the Theo Murphy meeting issue 'Macropinocytosis'.
DOI: 10.1098/rstb.2018.0157
PubMed: 30967006
PubMed Central: PMC6304739
Affiliations:
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Macropinocytosis may also convey information about the availability of extracellular nutrients to intracellular regulators of metabolism. Consistent with this idea, activation of the metabolic regulator mechanistic target of rapamycin complex-1 (mTORC1) in response to acute stimulation by growth factors and extracellular amino acids requires internalization of amino acids by macropinocytosis. This suggests that macropinocytosis is necessary for mTORC1-dependent growth of metazoan cells, both as a route for delivery of amino acids to sensors associated with lysosomes and as a platform for growth factor-dependent signalling to mTORC1 via phosphatidylinositol 3-kinase (PI3K) and the Akt pathway. Because the biochemical signals required for the construction of macropinosomes are also required for cell growth, and inhibition of macropinocytosis inhibits growth factor signalling to mTORC1, we propose that signalling by growth factor receptors is organized into stochastic, structure-dependent cascades of chemical reactions that both build a macropinosome and stimulate mTORC1. More generally, as discrete units of signal transduction, macropinosomes may be subject to feedback regulation by metabolism and cell dimensions. This article is part of the Theo Murphy meeting issue 'Macropinocytosis'.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">30967006</PMID><DateCompleted><Year>2020</Year><Month>01</Month><Day>21</Day></DateCompleted><DateRevised><Year>2020</Year><Month>05</Month><Day>15</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1471-2970</ISSN><JournalIssue CitedMedium="Internet"><Volume>374</Volume><Issue>1765</Issue><PubDate><Year>2019</Year><Month>02</Month><Day>04</Day></PubDate></JournalIssue><Title>Philosophical transactions of the Royal Society of London. 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This suggests that macropinocytosis is necessary for mTORC1-dependent growth of metazoan cells, both as a route for delivery of amino acids to sensors associated with lysosomes and as a platform for growth factor-dependent signalling to mTORC1 via phosphatidylinositol 3-kinase (PI3K) and the Akt pathway. Because the biochemical signals required for the construction of macropinosomes are also required for cell growth, and inhibition of macropinocytosis inhibits growth factor signalling to mTORC1, we propose that signalling by growth factor receptors is organized into stochastic, structure-dependent cascades of chemical reactions that both build a macropinosome and stimulate mTORC1. More generally, as discrete units of signal transduction, macropinosomes may be subject to feedback regulation by metabolism and cell dimensions. 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IdType="pubmed">17368443</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed><affiliations><list><country><li>États-Unis</li></country><region><li>Michigan</li></region></list><tree><country name="États-Unis"><region name="Michigan"><name sortKey="Swanson, Joel A" sort="Swanson, Joel A" uniqKey="Swanson J" first="Joel A" last="Swanson">Joel A. Swanson</name></region><name sortKey="Yoshida, Sei" sort="Yoshida, Sei" uniqKey="Yoshida S" first="Sei" last="Yoshida">Sei Yoshida</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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