Cross-talk between Remodeling and de Novo Pathways Maintains Phospholipid Balance through Ubiquitination*

Phosphatidylcholine (PtdCho), the major phospholipid of animal membranes, is generated by its remodeling and de novo synthesis. Overexpression of the remodeling enzyme, LPCAT1 (acyl-CoA:lysophosphatidylcholine acyltransferase) in epithelia decreased de novo PtdCho synthesis without significantly altering cellular PtdCho mass. Overexpression of LPCAT1 increased degradation of CPT1 (cholinephosphotransferase), a resident Golgi enzyme that catalyzes the terminal step for de novo PtdCho synthesis. CPT1 degradation involved its multiubiquitination and processing via the lysosomal pathway. CPT1 mutants harboring arginine substitutions at multiple carboxyl-terminal lysines exhibited proteolytic resistance to effects of LPCAT1 overexpression in cells and restored de novo PtdCho synthesis. Thus, cross-talk between phospholipid remodeling and de novo pathways involves ubiquitin-lysosomal processing of a key molecular target that mechanistically provides homeostatic control of cellular PtdCho content.

• Publication year

  2009

• Venue

  Journal of Biological Chemistry

• Publication date

  2009-12-15

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/jbc.M109.017350PMID 20018880PMCID PMC2825420
• 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.

• green fluorescent protein

  2020cited by this paper
• Masking of a Nuclear Signal Motif by Monoubiquitination Leads to Mislocalization and Degradation of the Regulatory Enzyme Cytidylyltransferase

  2009cited by this paper
• Mammalian acyl-CoA:lysophosphatidylcholine acyltransferase enzymes

  2008cited by this paper
• Lysosomal localization of ubiquitinated Jun requires multiple determinants in a lysine-27-linked polyubiquitin conjugate.

  2008cited by this paper
• Ubiquitin signals autophagic degradation of cytosolic proteins and peroxisomes

  2008cited by this paper
• Identification of a Novel Noninflammatory Biosynthetic Pathway of Platelet-activating Factor*

  2008cited by this paper
• PI4P promotes the recruitment of the GGA adaptor proteins to the trans-Golgi network and regulates their recognition of the ubiquitin sorting signal.

  2007cited by this paper
• Calmodulin Binds and Stabilizes the Regulatory Enzyme, CTP:Phosphocholine Cytidylyltransferase*

  2007cited by this paper
• Ubiquitin-dependent sorting of integral membrane proteins for degradation in lysosomes.

  2007cited by this paper
• Early Embryonic Lethality Caused by Disruption of the Gene for Choline Kinase α, the First Enzyme in Phosphatidylcholine Biosynthesis*

  2007cited by this paper
• Pseudomonas aeruginosa and sPLA2 IB stimulate ABCA1-mediated phospholipid efflux via ERK-activation of PPARalpha-RXR.

  2007cited by this paper
• A Single Enzyme Catalyzes Both Platelet-activating Factor Production and Membrane Biogenesis of Inflammatory Cells

  2007cited by this paper
• C-terminal modifications regulate MDM2 dissociation and nuclear export of p53

  2007cited by this paper
• Identification and characterization of a lysophosphatidylcholine acyltransferase in alveolar type II cells.

  2006cited by this paper
• A Rostrocaudal Muscular Dystrophy Caused by a Defect in Choline Kinase Beta, the First Enzyme in Phosphatidylcholine Biosynthesis*

  2006cited by this paper
• Transcriptional regulation of lung cytidylyltransferase in developing transgenic mice.

  2006cited by this paper
• Adenoviral gene transfer of a mutant surfactant enzyme ameliorates pseudomonas-induced lung injury

  2006cited by this paper
• Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain.

  2006cited by this paper
• Cloning and Characterization of Mouse Lung-type Acyl-CoA:Lysophosphatidylcholine Acyltransferase 1 (LPCAT1)

  2006cited by this paper
• Cloning and characterization a novel human 1-acyl-sn-glycerol-3-phosphate acyltransferase gene AGPAT7

  2005cited by this paper
• Ubiquitin-binding domains

  2005cited by this paper
• Oxysterols Inhibit Phosphatidylcholine Synthesis via ERK Docking and Phosphorylation of CTP:Phosphocholine Cytidylyltransferase*

  2005cited by this paper
• CTP:Phosphocholine Cytidylyltransferase: Paving the Way from Gene to Membrane*

  2005cited by this paper
• Golgi fragmentation is associated with ceramide-induced cellular effects.

  2005cited by this paper
• Membrane traffic: GGAs sort ubiquitin.

  2004cited by this paper
• Pulmonary Consequences of a Deep Breath Revisited

  2004cited by this paper
• Multiple monoubiquitination of RTKs is sufficient for their endocytosis and degradation

  2003cited by this paper
• The major sites of cellular phospholipid synthesis and molecular determinants of Fatty Acid and lipid head group specificity.

  2002cited by this paper
• Uncoupling Farnesol-induced Apoptosis from Its Inhibition of Phosphatidylcholine Synthesis*

  2001cited by this paper
• Tumor necrosis factor-alpha inhibits expression of CTP:phosphocholine cytidylyltransferase.

  2000cited by this paper
• Tumor Necrosis Factor-α Inhibits Expression of CTP:Phosphocholine Cytidylyltransferase*

  2000cited by this paper
• The expression of fatty acid synthase (FASE) is an early event in the development and progression of squamous cell carcinoma of the lung.

  2000cited by this paper
• Effects of intratracheal instillation of TNF-alpha on surfactant metabolism.

  2000cited by this paper
• Effects of intratracheal instillation of TNF-α on surfactant metabolism

  2000cited by this paper
• Cloning, Genomic Organization, and Characterization of a Human Cholinephosphotransferase*

  2000cited by this paper
• Inhibition of phosphatidylcholine and phosphatidylethanolamine biosynthesis in rat-2 fibroblasts by cell-permeable ceramides.

  1999cited by this paper
• A Conserved Histidine Is Essential for Glycerolipid Acyltransferase Catalysis

  1998cited by this paper
• The green fluorescent protein.

  1998cited by this paper
• CDP-choline:1,2-diacylglycerol cholinephosphotransferase.

  1997cited by this paper
• Role of acidic Ca2+-independent phospholipase A2 in synthesis of lung dipalmitoyl phosphatidylcholine.

  1997cited by this paper
• Betamethasone modulation of sphingomyelin hydrolysis up-regulates CTP:cholinephosphate cytidylyltransferase activity in adult rat lung.

  1996cited by this paper
• Expression of phosphatidylethanolamine N-methyltransferase-2 in McArdle-RH7777 hepatoma cells inhibits the CDP-choline pathway for phosphatidylcholine biosynthesis via decreased gene expression of CTP:phosphocholine cytidylyltransferase.

  1995cited by this paper
• Overexpression of rat liver CTP:phosphocholine cytidylyltransferase accelerates phosphatidylcholine synthesis and degradation.

  1994cited by this paper
• Phosphatidylcholine biosynthesis in Saccharomyces cerevisiae. Regulatory insights from studies employing null and chimeric sn-1,2-diacylglycerol choline- and ethanolaminephosphotransferases.

  1994cited by this paper
• Betamethasone activation of CTP:cholinephosphate cytidylyltransferase in vivo is lipid dependent.

  1994cited by this paper
• Regulation of CTP:choline-phosphate cytidylyltransferase by polyunsaturated n-3 fatty acids.

  1994cited by this paper
• Expression of Immunoreactive Cytidine 5′-Triphosphate: Cholinephosphate Cytidylyltransferase in Developing Rat Lung

  1993cited by this paper
• Evidence that the rate of phosphatidylcholine catabolism is regulated in cultured rat hepatocytes.

  1991cited by this paper
• Cytidylyltransferase translocation onto endoplasmic reticulum and increased de novo synthesis without phosphatidylcholine accumulation in Krebs-II ascite cells.

  1991cited by this paper
• Histamine stimulation of surfactant secretion from rat type II pneumocytes.

  1990cited by this paper
• Clearance and recycling of pulmonary surfactant.

  1990cited by this paper
• Structure-activity relations of the cardiac gap junction channel.

  1990cited by this paper
• The species of acyl-CoA in subcellular fractions of type II cells isolated from adult rat lung and their incorporation into phosphatidic acid.

  1989cited by this paper
• Molecular determinants of protein half‐lives in eukaryotic cells

  1987cited by this paper
• Synthesis of saturated phosphatidylcholine and phosphatidylglycerol by freshly isolated rat alveolar type II cells.

  1984cited by this paper
• The pulmonary consequences of a deep breath.

  1982cited by this paper
• Cholinephosphotransferase in rat lung. The in vitro synthesis of dipalmitoylphosphatidylcholine from dipalmitoylglycerol.

  1981cited by this paper
• Metabolism of glycerolipids. 2. The enzymatic acylation of lysolecithin.

  1960cited by this paper
• A rapid method of total lipid extraction and purification.

  1959cited by this paper

• Phosphatidylcholine Metabolism Controls Alveolar Progenitor Renewal and Pulmonary Fibrosis

  2025cites this paper
• HIF-2α/LPCAT1 orchestrates the reprogramming of lipid metabolism in ccRCC by modulating the FBXW7-mediated ubiquitination of ACLY

  2025cites this paper
• Metabolism Disruption Induced by High Ambient Temperature

  2024cites this paper
• LPCAT1 levels in the placenta, the maternal plasma and the fetal plasma do not predict fetal lung responses to glucocorticoids in a sheep model of pregnancy.

  2023cites this paper
• The daily caloric restriction and alternate-day fasting ameliorated lipid dysregulation in type 2 diabetic mice by downregulating hepatic pescadillo 1

  2022cites this paper
• Lipid–Protein and Protein–Protein Interactions in the Pulmonary Surfactant System and Their Role in Lung Homeostasis

  2020cites this paper
• Mosquito metabolomics reveal that dengue virus replication requires phospholipid reconfiguration via the remodeling cycle

  2020cites this paper
• Subcellular Organelles

  2019cites this paper
• Analysis of the regulation of surfactant phosphatidylcholine metabolism using stable isotopes.

  2017cites this paper
• Pulmonary surfactant metabolism in the alveolar airspace: Biogenesis, extracellular conversions, recycling.

  2017cites this paper
• RING finger E3 ligase PPP1R11 regulates TLR2 signaling and innate immunity

  2016cites this paper
• Factors Regulating the Substrate Specificity of A-type Phospholipases - A Mass-Spectrometric study

  2016cites this paper
• Membrane Biogenesis: Fatty Acids

  2016cites this paper
• Ubiquitin E3 ligase FIEL1 regulates fibrotic lung injury through SUMO-E3 ligase PIAS4

  2016cites this paper
• Models and Open Questions Pulmonary Surfactant Pathophysiology: Current

  2015cites this paper
• Steroid receptor coactivators 1 and 2 mediate fetal-to-maternal signaling that initiates parturition.

  2015cites this paper
• Cold Temperature Induces the Reprogramming of Proteolytic Pathways in Yeast*

  2015cites this paper
• The proinflammatory role of HECTD2 in innate immunity and experimental lung injury

  2015cites this paper
• Lysophosphatidylcholine Acyltransferase 1 (LPCAT1) Specifically Interacts with Phospholipid Transfer Protein StarD10 to Facilitate Surfactant Phospholipid Trafficking in Alveolar Type II Cells*

  2015cites this paper
• Lysophospholipid acyltransferases mediate phosphatidylcholine diversification to achieve the physical properties required in vivo.

  2014cites this paper
• Biogenesis of the multifunctional lipid droplet: Lipids, proteins, and sites

  2014influential citation
• Glycerophosphate/Acylglycerophosphate Acyltransferases

  2014cites this paper
• Glycerophospholipid and Sphingolipid Species and Mortality: The Ludwigshafen Risk and Cardiovascular Health (LURIC) Study

  2014cites this paper
• Two different pathways of phosphatidylcholine synthesis, the Kennedy Pathway and the Lands Cycle, differentially regulate cellular triacylglycerol storage

  2014influential citation
• The role of LPCAT in regulating cellular inflammatory responses to toll-like receptor ligands

  2014cites this paper
• Acyltransferases and transacylases that determine the fatty acid composition of glycerolipids and the metabolism of bioactive lipid mediators in mammalian cells and model organisms.

  2014cites this paper
• Targeting F Box Protein Fbxo3 To Control Cytokine-Driven Inflammation

  2013cites this paper
• Regulation of lung surfactant phospholipid synthesis and metabolism.

  2013cites this paper
• Acyl-CoA synthetase 3 promotes lipid droplet biogenesis in ER microdomains

  2013cites this paper
• Surfactant phospholipid metabolism.

  2013cites this paper
• Cytokine-Driven Inflammation Targeting F Box Protein Fbxo3 To Control

  2013cites this paper
• This information is current as Cytokine-Driven Inflammation Targeting F Box Protein Fbxo 3 To Control

  2013cites this paper
• Skp-cullin-F box E3 ligase component FBXL2 ubiquitinates Aurora B to inhibit tumorigenesis

  2013cites this paper
• Calmodulin protects Aurora B on the midbody to regulate the fidelity of cytokinesis

  2013cites this paper
• F-box protein FBXL2 targets cyclin D2 for ubiquitination and degradation to inhibit leukemic cell proliferation.

  2012cites this paper
• Human Lysophosphatidylcholine Acyltransferases 1 and 2 Are Located in Lipid Droplets Where They Catalyze the Formation of Phosphatidylcholine*

  2011cites this paper
• Physiological and molecular responses to dietary phospholipids vary between fry and early juvenile stages of rainbow trout (Oncorhynchus mykiss)

  2011cites this paper
• F box protein FBXL2 exerts human lung tumor suppressor-like activity by ubiquitin-mediated degradation of cyclin D3 resulting in cell cycle arrest

  2011cites this paper
• Enzymatic regulation of phosphatidylcholine synthesis via protein ubiquitination

  2010cites this paper
• Pulmonary surfactant pathophysiology: current models and open questions.

  2010cites this paper
• LPS Impairs Phospholipid Synthesis by Triggering β-Transducin Repeat-containing Protein (β-TrCP)-mediated Polyubiquitination and Degradation of the Surfactant Enzyme Acyl-CoA:Lysophosphatidylcholine Acyltransferase I (LPCAT1)*

  2010cites this paper
• Loss of lysophosphatidylcholine acyltransferase 1 leads to photoreceptor degeneration in rd11 mice

  2010cites this paper