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The Journal of Biological Chemistry Mar 2020An early exposure to lipid biochemistry in the laboratory of Konrad Bloch resulted in a fascination with the biosynthesis, structures, and functions of bacterial lipids....
An early exposure to lipid biochemistry in the laboratory of Konrad Bloch resulted in a fascination with the biosynthesis, structures, and functions of bacterial lipids. The discovery of plasmalogens (1-alk-1'-enyl, 2-acyl phospholipids) in anaerobic Gram-positive bacteria led to studies on the physical chemistry of these lipids and the cellular regulation of membrane lipid polymorphism in bacteria. Later studies in several laboratories showed that the formation of the alk-1-enyl ether bond involves an aerobic process in animal cells and thus is fundamentally different from that in anaerobic organisms. Our work provides evidence for an anaerobic process in which plasmalogens are formed from their corresponding diacyl lipids. Studies on the roles of phospholipases in revealed distinctions between its phospholipases and those previously discovered in other bacteria and showed how the enzymes are uniquely fitted to the intracellular lifestyle of this significant human pathogen.
Topics: Anaerobiosis; Bacteria, Anaerobic; Fatty Acids; Gram-Positive Bacteria; Lipids; Phosphatidylethanolamines; Plasmalogens
PubMed: 32221031
DOI: 10.1074/jbc.X120.013022 -
The Plant Cell Feb 2022Phosphatidic acid (PA) is an important lipid essential for several aspects of plant development and biotic and abiotic stress responses. We previously suggested that...
Phosphatidic acid (PA) is an important lipid essential for several aspects of plant development and biotic and abiotic stress responses. We previously suggested that submergence induces PA accumulation in Arabidopsis thaliana; however, the molecular mechanism underlying PA-mediated regulation of submergence-induced hypoxia signaling remains unknown. Here, we showed that in Arabidopsis, loss of the phospholipase D (PLD) proteins PLDα1 and PLDδ leads to hypersensitivity to hypoxia, but increased tolerance to submergence. This enhanced tolerance is likely due to improvement of PA-mediated membrane integrity. PA bound to the mitogen-activated protein kinase 3 (MPK3) and MPK6 in vitro and contributed to hypoxia-induced phosphorylation of MPK3 and MPK6 in vivo. Moreover, mpk3 and mpk6 mutants were more sensitive to hypoxia and submergence stress compared with wild type, and fully suppressed the submergence-tolerant phenotypes of pldα1 and pldδ mutants. MPK3 and MPK6 interacted with and phosphorylated RELATED TO AP2.12, a master transcription factor in the hypoxia signaling pathway, and modulated its activity. In addition, MPK3 and MPK6 formed a regulatory feedback loop with PLDα1 and/or PLDδ to regulate PLD stability and submergence-induced PA production. Thus, our findings demonstrate that PA modulates plant tolerance to submergence via both membrane integrity and MPK3/6-mediated hypoxia signaling in Arabidopsis.
Topics: Arabidopsis; Arabidopsis Proteins; DNA-Binding Proteins; Hypoxia; Mitogen-Activated Protein Kinase Kinases; Mitogen-Activated Protein Kinases; Mutation; Phenotype; Phosphatidic Acids; Phospholipase D; Plants, Genetically Modified; Protein Stability; Transcription Factors
PubMed: 34850198
DOI: 10.1093/plcell/koab289 -
Plant Biology (Stuttgart, Germany) May 2021Phosphatidic acid (PA) and hydrogen peroxide (H O ) play roles in regulating plant responses to abiotic stress. The objective of this study was to determine effects of H...
Phosphatidic acid (PA) and hydrogen peroxide (H O ) play roles in regulating plant responses to abiotic stress. The objective of this study was to determine effects of H O or PA, individually and interactively, with a H O scavenging molecule, N,N'-dimethylthoiurea (DMTU), on plant tolerance to heat stress in tall fescue (Festuca arundinacea). Plants were treated with PA (25 µm), H O (5 mm) and PA (25 µm) + DMTU (5 mm) by foliar application and then exposed to heat stress (38/33 °C) or optimal temperature (23/18 °C, day/night) for 28 days. Foliar application of PA and H O alone resulted in increases in leaf fresh weight, chlorophyll content, photochemical efficiency and cellular membrane stability in plants exposed to heat stress, whereas addition of DMTU suppressed the positive effects of PA. Expression levels of genes encoding the PA synthesizing enzyme, FaPLDδ, were significantly up-regulated by H O . Phosphatidic acid- or H O -enhanced heat tolerance was associated with the activation of stress signalling components (FaCDPK3, FaMPK6, FaMPK3), transcription factors (FaMBF1 and FaHsfA2c) and heat shock proteins (FaHSP18, FaHSP70 and FaHSP90). Phosphatidic acid and H O may work in coordination to further improve heat tolerance, involving up-regulation of transcription factors in stress signalling cascades and heat protection systems.
Topics: Festuca; Heat-Shock Response; Hydrogen Peroxide; Phosphatidic Acids; Thermotolerance
PubMed: 33188719
DOI: 10.1111/plb.13215 -
Traffic (Copenhagen, Denmark) Oct 2021Ligand-independent epidermal growth factor receptor (EGFR) endocytosis is inducible by a variety of stress conditions converging upon p38 kinase. A less known pathway...
Ligand-independent epidermal growth factor receptor (EGFR) endocytosis is inducible by a variety of stress conditions converging upon p38 kinase. A less known pathway involves phosphatidic acid (PA) signaling toward the activation of type 4 phosphodiesterases (PDE4) that decrease cAMP levels and protein kinase A (PKA) activity. This PA/PDE4/PKA pathway is triggered with propranolol used to inhibit PA hydrolysis and induces clathrin-dependent and clathrin-independent endocytosis, followed by reversible accumulation of EGFR in recycling endosomes. Here we give further evidence of this signaling pathway using biosensors of PA, cAMP, and PKA in live cells and then show that it activates p38 and ERK1/2 downstream the PKA inhibition. Clathrin-silencing and IN/SUR experiments involved the activity of p38 in the clathrin-dependent route, while ERK1/2 mediates clathrin-independent EGFR endocytosis. The PA/PDE4/PKA pathway selectively increases the EGFR endocytic rate without affecting LDLR and TfR constitute endocytosis. This selectiveness is probably because of EGFR phosphorylation, as detected in Th1046/1047 and Ser669 residues. The EGFR accumulates at perinuclear recycling endosomes colocalizing with TfR, fluorescent transferrin, and Rab11, while a small proportion distributes to Alix-endosomes. A non-selective recycling arrest includes LDLR and TfR in a reversible manner. The PA/PDE4/PKA pathway involving both p38 and ERK1/2 expands the possibilities of EGFR transmodulation and interference in cancer.
Topics: Clathrin; Endocytosis; ErbB Receptors; Ligands; MAP Kinase Signaling System; Phosphatidic Acids; Phosphorylation; Signal Transduction
PubMed: 34431177
DOI: 10.1111/tra.12812 -
EMBO Reports Oct 2021Phospholipase D (PLD) hydrolyzes membrane lipids to produce phosphatidic acid (PA), a lipid mediator involved in various cellular and physiological processes. Here, we...
Phospholipase D (PLD) hydrolyzes membrane lipids to produce phosphatidic acid (PA), a lipid mediator involved in various cellular and physiological processes. Here, we show that PLDα6 and PA regulate the distribution of GIBBERELLIN (GA)-INSENSITIVE DWARF1 (GID1), a soluble gibberellin receptor in rice. PLDα6-knockout (KO) plants display less sensitivity to GA than WT, and PA restores the mutant to a normal GA response. PA binds to GID1, as documented by liposome binding, fat immunoblotting, and surface plasmon resonance. Arginines 79 and 82 of GID1 are two key amino acid residues required for PA binding and also for GID1's nuclear localization. The loss of PLDα6 impedes GA-induced nuclear localization of GID1. In addition, PLDα6-KO plants attenuated GA-induced degradation of the DELLA protein SLENDER RICE1 (SLR1). These data suggest that PLDα6 and PA positively mediate GA signaling in rice via PA binding to GID1 and promotion of its nuclear translocation.
Topics: Gene Expression Regulation, Plant; Gibberellins; Mutation; Oryza; Phosphatidic Acids; Phospholipases; Plant Growth Regulators; Plant Proteins; Plants, Genetically Modified
PubMed: 34396669
DOI: 10.15252/embr.202051871 -
Methods in Molecular Biology (Clifton,... 20231-stearoyl (18:0)-2-arachidoyl (20:0)-sn-glycero-3-phospho-ß-D-glucoside (Phosphatidylglucoside or PtdGlc) was synthesized by direct coupling of D-glucose with the...
1-stearoyl (18:0)-2-arachidoyl (20:0)-sn-glycero-3-phospho-ß-D-glucoside (Phosphatidylglucoside or PtdGlc) was synthesized by direct coupling of D-glucose with the phosphate group of phosphatidic acid (18:0, 20:0). Selective in situ activation of the anomeric center of D-glucose by 2-chloro-1,3-dimethylimidazolinium chloride (DMC) in aqueous media allows the omission of protecting groups while furnishing the required ß-phosphate linkage with high selectivity. The described method is suitable to access PtdGlc in mg scale utilizing a simple two step purification protocol.
Topics: Glycerophospholipids; Glucose; Glucosides
PubMed: 36587071
DOI: 10.1007/978-1-0716-2910-9_6 -
Advances in Biological Regulation Jan 2021Lipids have emerged as important actors in an ever-growing number of key functions in cell biology over the last few years. Among them, glycerophospholipids are major... (Review)
Review
Lipids have emerged as important actors in an ever-growing number of key functions in cell biology over the last few years. Among them, glycerophospholipids are major constituents of cellular membranes. Because of their amphiphilic nature, phospholipids form lipid bilayers that are particularly useful to isolate cellular content from the extracellular medium, but also to define intracellular compartments. Interestingly, phospholipids come in different flavors based on their fatty acyl chain composition. Indeed, lipidomic analyses have revealed the presence in cellular membranes of up to 50 different species of an individual class of phospholipid, opening the possibility of multiple functions for a single class of phospholipid. In this review we will focus on phosphatidic acid (PA), the simplest phospholipid, that plays both structural and signaling functions. Among the numerous roles that have been attributed to PA, a key regulatory role in secretion has been proposed in different cell models. We review here the evidences that support the idea that mono- and poly-unsaturated PA control distinct steps in hormone secretion from neuroendocrine cells.
Topics: Animals; Biological Transport; Cell Membrane; Exocytosis; Humans; Neuroendocrine Cells; Phosphatidic Acids; Signal Transduction
PubMed: 33288473
DOI: 10.1016/j.jbior.2020.100772 -
Journal of Sports Sciences Feb 2022Phosphatidic acid (PA) is a lipid mediator proposed to increase muscle protein synthesis via direct stimulation of the mammalian target of rapamycin (mTOR) and may act... (Review)
Review
Phosphatidic acid (PA) is a lipid mediator proposed to increase muscle protein synthesis via direct stimulation of the mammalian target of rapamycin (mTOR) and may act as an anabolic supplemental aid. Evidence on the effectiveness of PA as an anabolic supplement is equivocal. We aimed to systematically assess the effect of PA on performance and body composition. Due to the small number of studies, this is a scoping review. A comprehensive search was performed in Pubmed, SPORTDiscus and Web of Science, from the 1 January 2010 to the 31 August 2020. Our search retrieved 2009 articles, which when filtered, resulted in six studies, published between 2012 and 2019, which were analysed further. Five studies were performed in adult male populations and one in an elderly male population. From these, three studies suggested no effect of PA on lean body mass , while the remaining showed a possible positive effect (body composition and performance improvements). In one of these, the supplement included other potentially anabolic substances, precluding an isolated effect of PA. After a thorough analysis of the studies included, the evidence does not support the supplementation with PA to increase performance or improve body composition in young or elderly men.
Topics: Adult; Aged; Body Composition; Dietary Supplements; Humans; Male; Muscle Proteins; Phosphatidic Acids
PubMed: 34706625
DOI: 10.1080/02640414.2021.1994769 -
Advances in Biological Regulation Jan 2020Diacylglycerol kinases (DGKs) contribute to an important part of intracellular signaling because, in addition to reducing diacylglycerol levels, they generate... (Review)
Review
Diacylglycerol kinases (DGKs) contribute to an important part of intracellular signaling because, in addition to reducing diacylglycerol levels, they generate phosphatidic acid (PtdOH) Recent research has led to the discovery of ten mammalian DGK isoforms, all of which are found in the mammalian brain. Many of these isoforms have studied functions within the brain, while others lack such understanding in regards to neuronal roles, regulation, and structural dynamics. However, while previously a neuronal function for DGKθ was unknown, it was recently found that DGKθ is required for the regulation of synaptic vesicle endocytosis and work is currently being conducted to elucidate the mechanism behind this regulation. Here we will review some of the roles of all mammalian DGKs and hypothesize additional roles. We will address the topic of redundancy among the ten DGK isoforms and discuss the possibility that DGKθ, among other DGKs, may have unstudied postsynaptic functions. We also hypothesize that in addition to DGKθ's presynaptic endocytic role, DGKθ might also regulate the endocytosis of AMPA receptors and other postsynaptic membrane proteins.
Topics: Animals; Diacylglycerol Kinase; Endocytosis; Humans; Isoenzymes; Mice; Neurons; Phosphatidic Acids; Receptors, AMPA; Synaptic Membranes; Synaptic Vesicles
PubMed: 31836314
DOI: 10.1016/j.jbior.2019.100688 -
Essays in Biochemistry Sep 2020Lipids function not only as the major structural components of cell membranes, but also as molecular messengers that transduce signals to trigger downstream signaling... (Review)
Review
Lipids function not only as the major structural components of cell membranes, but also as molecular messengers that transduce signals to trigger downstream signaling events in the cell. Phosphatidic acid (PA), the simplest and a minor class of glycerophospholipids, is a key intermediate for the synthesis of membrane and storage lipids, and also plays important roles in mediating diverse cellular and physiological processes in eukaryotes ranging from microbes to mammals and higher plants. PA comprises different molecular species that can act differently, and is found in virtually all organisms, tissues, and organellar membranes, with variations in total content and molecular species composition. The cellular levels of PA are highly dynamic in response to stimuli and multiple enzymatic reactions can mediate its production and degradation. Moreover, its unique physicochemical properties compared with other glycerophospholipids allow PA to influence membrane structure and dynamics, and interact with various proteins. PA has emerged as a class of new lipid mediators modulating various signaling and cellular processes via its versatile effects, such as membrane tethering, conformational changes, and enzymatic activities of target proteins, and vesicular trafficking.
Topics: Animals; Arabidopsis; Cell Membrane; Escherichia coli; Humans; Phosphatidic Acids; Phospholipase D; Proteins; Saccharomyces cerevisiae; Signal Transduction
PubMed: 32602549
DOI: 10.1042/EBC20190089