title: How phosphoinositide 3-phosphate controls growth downstream of amino acids and autophagy downstream of amino acid withdrawal.
abstract: 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.
authors.affiliation: Signalling Programme, Babraham Institute, Cambridge CB22 3AT, UK. nicholas.ktistakis@bbsrc.ac.uk
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Ktistakis
authors.forename: Maria
authors.initials: M
authors.lastname: Manifava
authors.forename: Priya
authors.initials: P
authors.lastname: Schoenfelder
authors.forename: Sergio
authors.initials: S
authors.lastname: Rotondo
mesh_terms: D000596:Amino Acids / Q000172:deficiency / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D049109:Cell Proliferation; D058546:Class III Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D010716:Phosphatidylinositols / Q000378:metabolism / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
chemical_list: D000596:Amino Acids; D046912:Multiprotein Complexes; D010716:Phosphatidylinositols; D011506:Proteins; C483312:phosphoinositide 3-phosphate; D058546:Class III Phosphatidylinositol 3-Kinases; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases