The simple phosphoinositide PtdIns3P has been shown to control cell growth downstream of amino acid signalling and autophagy downstream of amino acid withdrawal. These opposing effects depend in part on the existence of distinct complexes of Vps34 (vacuolar protein sorting 34), the kinase responsible for the majority of PtdIns3P synthesis in cells: one complex is activated after amino acid withdrawal to induce autophagy and another regulates mTORC1 (mammalian target of rapamycin complex 1) activation when amino acids are present. However, lipid-dependent signalling almost always exhibits a spatial dimension, related to the site of formation of the lipid signal. In the case of PtdIns3P-regulated autophagy induction, recent data suggest that PtdIns3P accumulates in a membrane compartment dynamically connected to the endoplasmic reticulum that constitutes a platform for the formation of some autophagosomes. For PtdIns3P-regulated mTORC1 activity, a spatial context is not yet known: several possibilities can be envisaged based on the known effects of PtdIns3P on the endocytic system and on recent data suggesting that activation of mTORC1 depends on its localization on lysosomes.
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February 2012
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Conference Article|
January 19 2012
How phosphoinositide 3-phosphate controls growth downstream of amino acids and autophagy downstream of amino acid withdrawal
Nicholas T. Ktistakis;
Nicholas T. Ktistakis
1
1Signalling Programme, Babraham Institute, Cambridge CB22 3AT, U.K.
1To whom correspondence should be addressed (email nicholas.ktistakis@bbsrc.ac.uk).
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Maria Manifava;
Maria Manifava
1Signalling Programme, Babraham Institute, Cambridge CB22 3AT, U.K.
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Priya Schoenfelder;
Priya Schoenfelder
1Signalling Programme, Babraham Institute, Cambridge CB22 3AT, U.K.
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Sergio Rotondo
Sergio Rotondo
1Signalling Programme, Babraham Institute, Cambridge CB22 3AT, U.K.
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Publisher: Portland Press Ltd
Received:
August 03 2011
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem Soc Trans (2012) 40 (1): 37–43.
Article history
Received:
August 03 2011
Citation
Nicholas T. Ktistakis, Maria Manifava, Priya Schoenfelder, Sergio Rotondo; How phosphoinositide 3-phosphate controls growth downstream of amino acids and autophagy downstream of amino acid withdrawal. Biochem Soc Trans 1 February 2012; 40 (1): 37–43. doi: https://doi.org/10.1042/BST20110684
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