Roles for PI(3,5)P2 in nutrient sensing through TORC1

The protein kinase TORC1 regulates cell growth in response to nutrients. This study demonstrates that phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) is a critical upstream modulator of TORC1 activity in yeast. In this capacity, PI(3,5)P2 is required for TORC1-dependent regulation of autophagy and nutrient-dependent endocytosis.

• Publication year

  2014

• Venue

  Molecular Biology of the Cell

• Publication date

  2014-04-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1091/mbc.E14-01-0021PMID 24478451PMCID 3967979
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Phosphatidylinositol 3,5‐bisphosphate: Low abundance, high significance

  2014cited by this paper
• Rag GTPases mediate amino acid–dependent recruitment of TFEB and MITF to lysosomes

  2013influential reference
• Yunis-Varón syndrome is caused by mutations in FIG4, encoding a phosphoinositide phosphatase.

  2013cited by this paper
• Inhibition of PIKfyve by YM-201636 Dysregulates Autophagy and Leads to Apoptosis-Independent Neuronal Cell Death

  2013cited by this paper
• A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB

  2012cited by this paper
• Structural and functional characterization of the two phosphoinositide binding sites of PROPPINs, a β-propeller protein family

  2012cited by this paper
• In vivo, Pikfyve generates PI(3,5)P2, which serves as both a signaling lipid and the major precursor for PI5P

  2012cited by this paper
• Phosphatidylinositol 3,5-bisphosphate plays a role in the activation and subcellular localization of mechanistic target of rapamycin 1

  2012influential reference
• Two-site recognition of phosphatidylinositol 3-phosphate by PROPPINs in autophagy.

  2012cited by this paper
• Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival

  2012cited by this paper
• Structure-based Analyses Reveal Distinct Binding Sites for Atg2 and Phosphoinositides in Atg18*

  2012cited by this paper
• mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway.

  2011cited by this paper
• TFEB, a novel mTORC1 effector implicated in lysosome biogenesis, endocytosis and autophagy

  2011cited by this paper
• Target of Rapamycin (TOR) in Nutrient Signaling and Growth Control

  2011influential reference
• mTORC1 Senses Lysosomal Amino Acids Through an Inside-Out Mechanism That Requires the Vacuolar H+-ATPase

  2011influential reference
• TORC1 regulates endocytosis via Npr1-mediated phosphoinhibition of a ubiquitin ligase adaptor.

  2011cited by this paper
• mTORC 1 Senses Lysosomal Amino Acids Through an Inside-Out Mechanism That Requires the Vacuolar H +-ATPase

  2011cited by this paper
• Structural conservation of components in the amino acid sensing branch of the TOR pathway in yeast and mammals.

  2010cited by this paper
• Structure of the human mTOR complex I and its implications for rapamycin inhibition.

  2010cited by this paper
• Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids.

  2010influential reference
• Roles of the Lipid-binding Motifs of Atg18 and Atg21 in the Cytoplasm to Vacuole Targeting Pathway and Autophagy*

  2010cited by this paper
• Tor Directly Controls the Atg1 Kinase Complex To Regulate Autophagy

  2009influential reference
• Sfp1 interaction with TORC1 and Mrs6 reveals feedback regulation on TOR signaling.

  2009cited by this paper
• PIKfyve Regulation of Endosome-Linked Pathways

  2009cited by this paper
• mTOR signaling at a glance

  2009cited by this paper
• Phosphatidylinositol 3,5-bisphosphate and Fab1p/PIKfyve underPPIn endo-lysosome function.

  2009cited by this paper
• Defective autophagy in neurons and astrocytes from mice deficient in PI(3,5)P2

  2009cited by this paper
• Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy.

  2009cited by this paper
• Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALS.

  2009cited by this paper
• The Vam6 GEF controls TORC1 by activating the EGO complex.

  2009influential reference
• Dynamics and diversity in autophagy mechanisms: lessons from yeast

  2009cited by this paper
• RAG GTPases in nutrient-mediated TOR signaling pathway

  2009cited by this paper
• ArPIKfyve homomeric and heteromeric interactions scaffold PIKfyve and Sac3 in a complex to promote PIKfyve activity and functionality.

  2008cited by this paper
• A selective PIKfyve inhibitor blocks PtdIns(3,5)P2 production and disrupts endomembrane transport and retroviral budding

  2008cited by this paper
• Arrestin-related ubiquitin-ligase adaptors regulate endocytosis and protein turnover at the cell surface.

  2008cited by this paper
• Membrane recognition by phospholipid-binding domains

  2008cited by this paper
• The Atg18-Atg2 Complex Is Recruited to Autophagic Membranes via Phosphatidylinositol 3-Phosphate and Exerts an Essential Function*

  2008cited by this paper
• TOR1 and TOR2 Have Distinct Locations in Live Cells

  2008influential reference
• The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1

  2008cited by this paper
• Assembly of a Fab1 phosphoinositide kinase signaling complex requires the Fig4 phosphoinositide phosphatase.

  2008influential reference
• VAC14 nucleates a protein complex essential for the acute interconversion of PI3P and PI(3,5)P2 in yeast and mouse

  2008cited by this paper
• Efficient Tor Signaling Requires a Functional Class C Vps Protein Complex in Saccharomyces cerevisiae

  2007cited by this paper
• Atg18 regulates organelle morphology and Fab1 kinase activity independent of its membrane recruitment by phosphatidylinositol 3,5-bisphosphate.

  2007cited by this paper
• ESCRTs and Fab1 regulate distinct steps of autophagy.

  2007cited by this paper
• Sch9 is a major target of TORC1 in Saccharomyces cerevisiae.

  2007influential reference
• Loss of Vac14, a regulator of the signaling lipid phosphatidylinositol 3,5-bisphosphate, results in neurodegeneration in mice

  2007cited by this paper
• The Atg1 kinase complex is involved in the regulation of protein recruitment to initiate sequestering vesicle formation for nonspecific autophagy in Saccharomyces cerevisiae.

  2007cited by this paper
• Protein kinase A and Sch9 cooperatively regulate induction of autophagy in Saccharomyces cerevisiae.

  2007cited by this paper
• Mutation of FIG4 causes neurodegeneration in the pale tremor mouse and patients with CMT4J

  2007cited by this paper
• Determining selectivity of phosphoinositide-binding domains.

  2006cited by this paper
• The phosphoinositide kinase PIKfyve/Fab1p regulates terminal lysosome maturation in Caenorhabditis elegans.

  2006cited by this paper
• The Vac14p–Fig4p complex acts independently of Vac7p and couples PI3,5P2 synthesis and turnover

  2006influential reference
• Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice

  2006cited by this paper
• Phosphoinositide 5-Phosphatase Fig4p Is Required for both Acute Rise and Subsequent Fall in Stress-Induced Phosphatidylinositol 3,5-Bisphosphate Levels

  2006influential reference
• The Vac 14 p – Fig 4 p complex acts independently of Vac 7 p and couples PI 3 , 5 P 2 synthesis and turnover

  2006cited by this paper
• A conserved GTPase-containing complex is required for intracellular sorting of the general amino-acid permease in yeast

  2006cited by this paper
• The TOR and EGO protein complexes orchestrate microautophagy in yeast.

  2005cited by this paper
• LAS24/KOG1, a component of the TOR complex 1 (TORC1), is needed for resistance to local anesthetic tetracaine and normal distribution of actin cytoskeleton in yeast.

  2005cited by this paper
• The role of autophagy during the early neonatal starvation period

  2004cited by this paper
• Svp1p defines a family of phosphatidylinositol 3,5‐bisphosphate effectors

  2004cited by this paper
• TOR Complex 1 Includes a Novel Component, Tco89p (YPL180w), and Cooperates with Ssd1p to Maintain Cellular Integrity in Saccharomyces cerevisiae*

  2004cited by this paper
• Vacuole size control: regulation of PtdIns(3,5)P2 levels by the vacuole-associated Vac14-Fig4 complex, a PtdIns(3,5)P2-specific phosphatase.

  2003cited by this paper
• The Mammalian Target of Rapamycin (mTOR) Partner, Raptor, Binds the mTOR Substrates p70 S6 Kinase and 4E-BP1 through Their TOR Signaling (TOS) Motif*

  2003cited by this paper
• Vac14 controls PtdIns(3,5)P(2) synthesis and Fab1-dependent protein trafficking to the multivesicular body.

  2002cited by this paper
• Regulation of Fab1 phosphatidylinositol 3-phosphate 5-kinase pathway by Vac7 protein and Fig4, a polyphosphoinositide phosphatase family member.

  2002influential reference
• Osmotic stress–induced increase of phosphatidylinositol 3,5-bisphosphate requires Vac14p, an activator of the lipid kinase Fab1p

  2002influential reference
• Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control.

  2002influential reference
• Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action.

  2002cited by this paper
• mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery.

  2002cited by this paper
• Global Analysis of Protein Activities Using Proteome Chips

  2001cited by this paper
• Membrane Recruitment of Aut7p in the Autophagy and Cytoplasm to Vacuole Targeting Pathways Requires Aut1p, Aut2p, and the Autophagy Conjugation Complex

  2001cited by this paper
• Tripartite Regulation of Gln3p by TOR, Ure2p, and Phosphatases*

  2000cited by this paper
• The Itinerary of a Vesicle Component, Aut7p/Cvt5p, Terminates in the Yeast Vacuole via the Autophagy/Cvt Pathways*

  2000cited by this paper
• Formation Process of Autophagosome Is Traced with Apg8/Aut7p in Yeast

  1999cited by this paper
• Immunopurified Mammalian Target of Rapamycin Phosphorylates and Activates p70 S6 Kinase α in Vitro *

  1999cited by this paper
• A protein conjugation system essential for autophagy

  1998cited by this paper
• Fab1p Is Essential for PtdIns(3)P 5-Kinase Activity and the Maintenance of Vacuolar Size and Membrane Homeostasis

  1998cited by this paper
• RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1.

  1998cited by this paper
• The TOR nutrient signalling pathway phosphorylates NPR1 and inhibits turnover of the tryptophan permease

  1998influential reference
• Vac8p, a Vacuolar Protein with Armadillo Repeats, Functions in both Vacuole Inheritance and Protein Targeting from the Cytoplasm to Vacuole

  1998cited by this paper
• Acidification of vacuoles is required for autophagic degradation in the yeast, Saccharomyces cerevisiae.

  1997cited by this paper
• Vac7p, a novel vacuolar protein, is required for normal vacuole inheritance and morphology

  1997cited by this paper
• Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin.

  1997cited by this paper
• Regulation of eIF-4E BP1 Phosphorylation by mTOR*

  1997cited by this paper
• A new vital stain for visualizing vacuolar membrane dynamics and endocytosis in yeast

  1995cited by this paper
• Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast

  1991cited by this paper
• Regulation of compartmentation of amino acid pools in Saccharomyces cerevisiae and its effects on metabolic control.

  1980cited by this paper
• Sch 9 Is a Major Target of TORC 1 in Saccharomyces cerevisiae

  year unknowncited by this paper

• EGO complex at 20: The Rag GTPase-TORC1 nutrient-sensing blueprint.

  2026cites this paper
• Hyperosmotic Stress Promotes the Nuclear Translocation of TFEB in Tubular Epithelial Cells Depending on Intracellular Ca2+ Signals via TRPML Channels

  2025cites this paper
• Homeostatic Influence of Fig4 Outside of the Fab1‐Vac14‐Fig4 Complex in Saccharomyces cerevisiae

  2025cites this paper
• Mechanism of phosphoinositide regulation of lysosomal pH via inhibition of CLC-7

  2025cites this paper
• TORC1 autonomously controls its spatial partitioning via the Rag GTPase tether Tco89.

  2025cites this paper
• TOR signaling on membranes.

  2025cites this paper
• Regulatory dynamics of Sch9 in response to cytosolic acidification: From spatial reconfiguration to cellular adaptation to stresses

  2024cites this paper
• Assessing the Presence of Phosphoinositides on Autophagosomal Membrane in Yeast by Live Cell Imaging

  2024cites this paper
• PI(3,5)P2 asymmetry during mitosis is essential for asymmetric vacuolar inheritance

  2024cites this paper
• Membrane contact sites regulate vacuolar fission via sphingolipid metabolism

  2024cites this paper
• Synaptojanin1 Modifies Endolysosomal Parameters in Cultured Ventral Midbrain Neurons

  2023cites this paper
• The nutrient-responsive CDK Pho85 primes the Sch9 kinase for its activation by TORC1

  2023cites this paper
• Pib2 is a cysteine sensor involved in TORC1 activation in Saccharomyces cerevisiae.

  2023cites this paper
• Membrane contact sites regulate vacuolar fission via 1 sphingolipid metabolism 2 3

  2023cites this paper
• The signalling lipid PI3,5P2 is essential for timely mitotic exit

  2023cites this paper
• The Yeast Protein Kinase Sch9 Functions as a Central Nutrient-Responsive Hub That Calibrates Metabolic and Stress-Related Responses

  2023cites this paper
• Yck3 casein kinase-mediated phosphorylation determines Ivy1 localization and function at endosomes and vacuole.

  2023cites this paper
• Snf1/AMPK fine-tunes TORC1 signaling in response to glucose starvation

  2022cites this paper
• Synaptojanin1 regulates lysosomal functions in ventral midbrain neurons

  2022cites this paper
• Bur1 functions with TORC1 for vacuole‐mediated cell cycle progression

  2022cites this paper
• The Inositol Phosphate System—A Coordinator of Metabolic Adaptability

  2022cites this paper
• A conserved MTMR lipid phosphatase increasingly suppresses autophagy in brain neurons during aging

  2021cites this paper
• Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1

  2021cites this paper
• Nutrient transceptors physically interact with the yeast S6/protein kinase B homolog, Sch9, a TOR kinase target

  2021cites this paper
• Vacuolar localization via the N-terminal domain of Sch9 is required for TORC1-dependent phosphorylation and downstream signal transduction

  2021cites this paper
• Pib2 as an Emerging Master Regulator of Yeast TORC1

  2021cites this paper
• The spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorders due to defective autophagy

  2021cites this paper
• Phosphoinositides in cell proliferation and metabolism.

  2020cites this paper
• Nutrient transceptors physically interact with the yeast S 6 / Protein 1 kinase B homolog , Sch 9 , a TOR kinase target 2 3

  2020cites this paper
• A novel phosphoinositide kinase Fab1 regulates biosynthesis of pathogenic aflatoxin in Aspergillus flavus

  2020cites this paper
• TORC1 Determines Fab1 Lipid Kinase Function at Signaling Endosomes and Vacuoles.

  2020influential citation
• Sticking With It: ER-PM Membrane Contact Sites as a Coordinating Nexus for Regulating Lipids and Proteins at the Cell Cortex

  2020cites this paper
• Rab35-regulated lipid turnover by myotubularins represses mTORC1 activity and controls myelin growth

  2020cites this paper
• Phosphoinositides in the control of lysosome function and homeostasis.

  2019cites this paper
• Spatially Distinct Pools of TORC1 Balance Protein Homeostasis.

  2019influential citation
• Spatially distinct pools of TORC1 balance protein homeostasis

  2019cites this paper
• Interaction of the late endo-lysosomal lipid PI(3,5)P2 with the Vph1 isoform of yeast V-ATPase increases its activity and cellular stress tolerance

  2019cites this paper
• Phosphoinositides in autophagy: current roles and future insights

  2019cites this paper
• TORC1 regulates vacuole membrane composition through ubiquitin- and ESCRT-dependent microautophagy

  2019cites this paper
• TORC1 specifically inhibits microautophagy through ESCRT-0

  2019cites this paper
• Mechanisms and regulation of plasma membrane-endoplasmic reticulum Membrane Contact Sites in Saccharomyces cerevisiae

  2018cites this paper
• Control of vacuole membrane homeostasis by a resident PI-3,5-kinase inhibitor

  2018cites this paper
• A substrate localization model for the selective regulation of TORC1 downstream pathways

  2018cites this paper
• Ivy1 is a negative regulator of Gtr-dependent TORC1 activation

  2018cites this paper
• Spatially Distinct Pools of TORC 1 Balance Protein Homeostasis Graphical

  2018influential citation
• Cell Cycle Control by Cyclin-CDKS in Chlamydomonas ReinhardtII

  2018cites this paper
• Inhibition of PIP4Kγ ameliorates the pathological effects of mutant huntingtin protein

  2017cites this paper
• Regulation of Lysosomal Adaptation to Nutrient Starvation by Lysosomal TRPML1 and PIKfyve

  2017cites this paper
• An In Vitro TORC1 Kinase Assay That Recapitulates the Gtr-Independent Glutamine-Responsive TORC1 Activation Mechanism on Yeast Vacuoles

  2017influential citation
• Un niveau minimal d'un homologue potentiel de la phosphoinositide-phosphatase SAC1 chez "Plasmodium falciparum" semble requis pour assurer la survie durant le stade érythrocytaire asexué

  2017cites this paper
• Molecular mechanisms of myelin dysfunctions in the nervous system

  2017influential citation
• Phosphoinositide conversion in endocytosis and the endolysosomal system

  2017cites this paper
• Quantitative proteomics to study a small molecule targeting the loss of von Hippel–Lindau in renal cell carcinomas

  2017cites this paper
• ATP13A2/PARK9 regulates endo‐/lysosomal cargo sorting and proteostasis through a novel PI(3, 5)P2‐mediated scaffolding function

  2017cites this paper
• Regulation of autophagy by mitochondrial phospholipids in health and diseases.

  2017cites this paper
• DNA damage regulates direct association of TOR kinase with the RNA polymerase II–transcribed HMO1 gene

  2017cites this paper
• The yeast protein kinase Sch9 adjusts V-ATPase assembly/disassembly to control pH homeostasis and longevity in response to glucose availability

  2017cites this paper
• Ste12/Fab1 phosphatidylinositol-3-phosphate 5-kinase is required for nitrogen-regulated mitotic commitment and cell size control

  2017cites this paper
• pH homeostasis in yeast; the phosphate perspective

  2017cites this paper
• The two-pore channel TPC1 is required for efficient protein processing through early and recycling endosomes

  2017cites this paper
• Hygromycin B hypersensitive (hhy) mutants implicate an intact trans-Golgi and late endosome interface in efficient Tor1 vacuolar localization and TORC1 function

  2017cites this paper
• Membrane Phosphoproteomics of Yeast Early Response to Acetic Acid: Role of Hrk1 Kinase and Lipid Biosynthetic Pathways, in Particular Sphingolipids

  2017cites this paper
• PI5P and PI(3,5)P2: Minor, but Essential Phosphoinositides.

  2017cites this paper
• Vacuole-mediated selective regulation of TORC1-Sch9 signaling following oxidative stress

  2017influential citation
• Inhibition of PIP 4 K ameliorates the pathological effects of mutant huntingtin protein 1

  2017cites this paper
• Sphingolipid biosynthesis upregulation by TOR complex 2-Ypk1 signaling during yeast adaptive response to acetic acid stress.

  2016cites this paper
• Investigating novel interaction partners of amyloid precursor protein: the mechanistic target of rapamycin and pikyve complex

  2016cites this paper
• New insights into the functions of PtdIns(3,5)P2 in the pathogenisis of neurodegenerative disorders

  2016cites this paper
• Target of rapamycin signaling mediates vacuolar fragmentation

  2016influential citation
• Dynamic relocation of the TORC1–Gtr1/2–Ego1/2/3 complex is regulated by Gtr1 and Gtr2

  2016cites this paper
• Signalling 2015: Cellular Functions of Phosphoinositides and Inositol Phosphates Phosphatidylinositol 3,5-bisphosphate: regulation of cellular events in space and time

  2016cites this paper
• Phosphatidylinositol 3‐phosphates—at the interface between cell signalling and membrane traffic

  2016cites this paper
• Elucidating the Role of Phosphoinositides in Melanogenesis: PIKfyve Regulates Melanogenic Processes through the Synthesis of PI(3,5)P2 and PI(5)P

  2016influential citation
• Phosphoinositide‐binding proteins in autophagy

  2016cites this paper
• Dynamic Regulation of Phosphatidylinositol 3,5-bisphosphate and its Upstream Lipid Kinase Fab1/PIKfyve

  2016cites this paper
• Complex Relations Between Phospholipids, Autophagy, and Neutral Lipids.

  2016cites this paper
• Phosphatidylinositol 3,5-bisphosphate: regulation of cellular events in space and time.

  2016influential citation
• Phosphatidylinositol 3,5‐Bisphosphate‐Rich Membrane Domains in Endosomes and Lysosomes

  2016cites this paper
• TOR signalling in plants.

  2015cites this paper
• Phosphoinositides: Key modulators of energy metabolism.

  2015cites this paper
• Nuclear PI3K signaling in cell growth and tumorigenesis

  2015cites this paper
• PROTEIN KINASES AND PHOSPHATASES IN VACUOLE MEMBRANE PERMEABILIZATION

  2015cites this paper
• Studies on the response to, and recovery from, rapamycin in Saccharomyces cerevisiae

  2015influential citation
• A proteo-liposome system for the analysis of the intracellular interactome of membrane proteins using amyloid precursor protein as a model

  2015cites this paper
• A LAPF/phafin1-like protein regulates TORC1 and lysosomal membrane permeabilization in response to endoplasmic reticulum membrane stress

  2015cites this paper
• The vacuole/lysosome is required for cell-cycle progression

  2015influential citation
• Regulation of autophagy by amino acids and MTOR-dependent signal transduction

  2014cites this paper
• Growing knowledge of the mTOR signaling network.

  2014cites this paper
• Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

  2012cites this paper
• Membrane contact sites regulate vacuolar fission via 1 sphingolipid metabolism

  year unknowncites this paper