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Membrane Sterols

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https://www.readbyqxmd.com/read/28213130/dipeptidyl-peptidase-4-impairs-insulin-signalling-and-promotes-lipid-accumulation-in-hepatocytes
#1
Kerstin Rufinatscha, Bernhard Radlinger, Jochen Dobner, Sabrina Folie, Claudia Bon, Elisabeth Profanter, Claudia Ress, Karin Salzmann, Gabriele Staudacher, Herbert Tilg, Susanne Kaser
Dipeptidyl-peptidase 4 [DPP-4) has evolved into an important target in diabetes therapy due to its role in incretin hormone metabolism. In contrast to its systemic effects, cellular functions of membranous DPP-4 are less clear. Here we studied the role of DPP-4 in hepatic energy metabolism. In order to distinguish systemic from cellular effects we established a cell culture model of DPP-4 knockdown in human hepatoma cell line HepG2. DPP-4 suppression was associated with increased basal glycogen content due to enhanced insulin signalling as shown by increased phosphorylation of insulin-receptor substrate 1 (IRS-1), protein kinase B/Akt and mitogen-activated protein kinases (MAPK)/ERK, respectively...
February 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28209730/role-of-stard4-in-sterol-transport-between-the-endocytic-recycling-compartment-and-the-plasma-membrane
#2
David B Iaea, Shu Mao, Frederik W Lund, Frederick R Maxfield
Cholesterol is an essential constituent of membranes in mammalian cells. The plasma membrane and the endocytic recycling compartment (ERC) are both highly enriched in cholesterol. The abundance and distribution of cholesterol among organelles are tightly controlled by a combination of mechanisms involving vesicular and non-vesicular sterol transport processes. Using the fluorescent cholesterol analog, dehydroergosterol, we examined sterol transport between the plasma membrane and the ERC using fluorescence recovery after photobleaching and a novel sterol efflux assay...
February 16, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28205176/determining-the-topology-of-membrane-bound-proteins-using-pegylation
#3
Vicky Howe, Andrew J Brown
Biochemical methods can help elucidate the membrane topology of hydrophobic membrane proteins where X-ray crystallography is difficult or impractical, providing important structural data. Here, we describe the method of PEGylation, which uses a cysteine-reactive molecule, maleimide polyethylene glycol (mPEG), to determine the cytosolic accessibility of introduced cysteine residues. This accessibility is visualized using Western blotting to detect a band shift that indicates cysteine labeling by mPEG. Using scanning cysteine mutagenesis, followed by PEGylation, one can map the accessibility of the introduced cysteines, hence inferring the membrane topology of the protein...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28205171/synthesis-and-live-cell-imaging-of-fluorescent-sterols-for-analysis-of-intracellular-cholesterol-transport
#4
Maciej Modzel, Frederik W Lund, Daniel Wüstner
Cellular cholesterol homeostasis relies on precise control of the sterol content of organelle membranes. Obtaining insight into cholesterol trafficking pathways and kinetics by live-cell imaging relies on two conditions. First, one needs to develop suitable analogs that resemble cholesterol as closely as possible with respect to their biophysical and biochemical properties. Second, the cholesterol analogs should have good fluorescence properties. This interferes, however, often with the first requirement, such that the imaging instrumentation must be optimized to collect photons from suboptimal fluorophores, but good cholesterol mimics, such as the intrinsically fluorescent sterols, cholestatrienol (CTL) or dehydroergosterol (DHE)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28205170/transport-assays-for-sterol-binding-proteins-stopped-flow-fluorescence-methods-for-investigating-intracellular-cholesterol-transport-mechanisms-of-npc2-protein
#5
Leslie A McCauliff, Judith Storch
In this chapter we describe the use of stopped flow fluorescence spectroscopy to analyze the kinetic mechanisms of protein mediated cholesterol transfer to, from, and between model membranes. These assays allow for the detection of protein-membrane interactions that may occur during cholesterol transfer by simply modifying donor or acceptor concentrations, membrane composition, or buffer properties, and analyzing resultant transfer rates.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28203225/regulation-of-sterol-biosynthesis-in-the-human-fungal-pathogen-aspergillus-fumigatus-opportunities-for-therapeutic-development
#6
REVIEW
Sourabh Dhingra, Robert A Cramer
Sterols are a major component of eukaryotic cell membranes. For human fungal infections caused by the filamentous fungus Aspergillus fumigatus, antifungal drugs that target sterol biosynthesis and/or function remain the standard of care. Yet, an understanding of A. fumigatus sterol biosynthesis regulatory mechanisms remains an under developed therapeutic target. The critical role of sterol biosynthesis regulation and its interactions with clinically relevant azole drugs is highlighted by the basic helix loop helix (bHLH) class of transcription factors known as Sterol Regulatory Element Binding Proteins (SREBPs)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28202541/coordinate-regulation-of-yeast-sterol-regulatory-element-binding-protein-srebp-and-mga2-transcription-factors
#7
Risa Burr, Emerson V Stewart, Peter J Espenshade
The Mga2 and Sre1 transcription factors regulate oxygen-responsive lipid homeostasis in the fission yeast Schizosaccharomyces pombe in a manner analogous to the mammalian Sterol Regulatory Element-Binding Protein transcription factors SREBP-1 and SREBP-2. Mga2 and SREBP-1 regulate triacylglycerol and glycerophospholipid synthesis, while Sre1 and SREBP-2 regulate sterol synthesis. In mammals, a shared activation mechanism allows for coordinate regulation of SREBP-1 and SREBP-2. In contrast, distinct pathways activate fission yeast Mga2 and Sre1...
February 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28191915/routes-and-mechanisms-of-post-endosomal-cholesterol-trafficking-a-story-that-never-ends
#8
REVIEW
Jie Luo, Luyi Jiang, Hongyuan Yang, Bao-Liang Song
Mammalian cells acquire most exogenous cholesterol through receptor-mediated endocytosis of low-density lipoproteins (LDLs). After internalization, LDL cholesteryl esters are hydrolyzed to release free cholesterol, which then translocates to late endosomes (LEs)/lysosomes (LYs) and incorporates into the membranes by coordinated actions of Niemann-Pick type C (NPC) 1 and NPC2 proteins. However, how cholesterol exits LEs/LYs and moves to other organelles remain largely unclear. Growing evidence has suggested that nonvesicular transport is critically involved in the post-endosomal cholesterol trafficking...
February 13, 2017: Traffic
https://www.readbyqxmd.com/read/28187768/current-lipid-extraction-methods-are-significantly-enhanced-adding-a-water-treatment-step-in-chlorella-protothecoides
#9
Xiaojie Ren, Xinhe Zhao, François Turcotte, Jean-Sébastien Deschênes, Réjean Tremblay, Mario Jolicoeur
BACKGROUND: Microalgae have the potential to rapidly accumulate lipids of high interest for the food, cosmetics, pharmaceutical and energy (e.g. biodiesel) industries. However, current lipid extraction methods show efficiency limitation and until now, extraction protocols have not been fully optimized for specific lipid compounds. The present study thus presents a novel lipid extraction method, consisting in the addition of a water treatment of biomass between the two-stage solvent extraction steps of current extraction methods...
February 11, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28184226/clathrin-in-chara-australis-molecular-analysis-and-involvement-in-charasome-degradation-and-constitutive-endocytosis
#10
Marion C Hoepflinger, Margit Hoeftberger, Aniela Sommer, Christina Hametner, Ilse Foissner
Charasomes are convoluted plasma membrane domains in characean green algae. They are known to form in response to light via secretion of trans-Golgi network (TGN) vesicles and local inhibition of endocytosis. Charasomes are involved in the acidification of their aqueous environment, thereby facilitating photosynthesis-dependent carbon uptake. Charasome formation is reversible to allow cells to adapt to different light conditions. Here, we show that darkness-induced degradation of charasomes involves the formation of coated pits and coated vesicles...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28111289/ancient-highly-conserved-proteins-from-a-luca-with-complex-cell-biology-provide-evidence-in-support-of-the-nuclear-compartment-commonality-nucom-hypothesis
#11
REVIEW
James T Staley, John A Fuerst
The nuclear compartment commonality (NuCom) hypothesis posits a complex last common ancestor (LUCA) with membranous compartments including a nuclear membrane. Such a LUCA then evolved to produce two nucleated lineages of the tree of life: the Planctomycetes-Verrucomicrobia-Chlamydia superphylum (PVC) within the Bacteria, and the Eukarya. We propose that a group of ancient essential protokaryotic signature proteins (PSPs) originating in LUCA were incorporated into ancestors of PVC Bacteria and Eukarya. Tubulins, ubiquitin system enzymes and sterol-synthesizing enzymes are consistent with early origins of these features shared between the PVC superphylum and Eukarya...
January 19, 2017: Research in Microbiology
https://www.readbyqxmd.com/read/28109215/interplay-between-alkyl-chain-asymmetry-and-cholesterol-addition-in-the-rigid-ion-pair-amphiphile-bilayer-systems
#12
Fong-Yin Huang, Chi-Cheng Chiu
Ion pair amphiphile (IPA), a molecular complex composed of a pair of cationic and anionic surfactants, has been proposed as a novel phospholipid substitute. Controlling the physical stability of IPA vesicles is important for its application developments such as cosmetic and drug deliveries. To investigate the effects of IPA alkyl chain combinations and the cholesterol additive on the structural and mechanical properties of IPA vesicular bilayers, we conducted a series of molecular dynamics studies on the hexadecyltrimethylammonium-dodecylsulfate (HTMA-DS) and dodecyltrimethylammonium-hexadecylsulfate (DTMA-HS) IPA bilayers with cholesterol...
January 21, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28107409/targeted-deletion-of-a-plasmodium-site-2-protease-impairs-life-cycle-progression-in-the-mammalian-host
#13
Konstantinos Koussis, Evi Goulielmaki, Anna Chalari, Chrislaine Withers-Martinez, Inga Siden-Kiamos, Kai Matuschewski, Thanasis G Loukeris
Site-2 proteases (S2P) belong to the M50 family of metalloproteases, which typically perform essential roles by mediating activation of membrane-bound transcription factors through regulated intramembrane proteolysis (RIP). Protease-dependent liberation of dormant transcription factors triggers diverse cellular responses, such as sterol regulation, Notch signalling and the unfolded protein response. Plasmodium parasites rely on regulated proteolysis for controlling essential pathways throughout the life cycle...
2017: PloS One
https://www.readbyqxmd.com/read/28104494/thoughts-on-interactions-between-pgrmc1-and-diverse-attested-and-potential-hydrophobic-ligands
#14
REVIEW
Michael A Cahill, Amy E Medlock
Progesterone Receptor Membrane Component 1 (PGRMC1) is located in many different subcellular locations with many different attested and probably location-specific functions. PGRMC1 was recently identified in the mitochondrial outer membrane where it interacts with ferrochelatase, the last enzyme in the heme synthetic pathway. It has been proposed that PGRMC1 may act as a chaperone to shuttle newly synthesized heme from the mitochondrion to cytochrome P450 (cyP450) enzymes. Here we consider potential roles that PGRMC1 may play in transferring heme, and other small hydrophobic ligands such as cholesterol and steroids, between the hydrophobic compartment of the membrane lipid bilayer interior to aqueous proteins, and perhaps to the membranes of other organelles...
January 16, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28100609/sterol-binding-by-the-tombusviral-replication-proteins-is-essential-for-replication-in-yeast-and-plants
#15
Kai Xu, Peter D Nagy
: Membranous structures derived from various organelles are important for replication of plus-stranded RNA viruses. Although the important roles of co-opted host proteins in RNA virus replication have been appreciated for a decade, the equally important functions of cellular lipids in virus replication are gaining full attention only recently. Previous works with Tomato bushy stunt tombusvirus (TBSV) in model host yeast have revealed essential roles for phosphatidylethanolamine and sterols in viral replication...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28096191/allosteric-modulation-of-the-substrate-specificity-of-acyl-coa-wax-alcohol-acyltransferase-2-awat2
#16
Jason M Arne, Made Airanthi K Widjaja-Adhi, Taylor Hughes, Kevin W Huynh, Josie A Silvaroli, Sylwia Chelstowska, Vera Y Moiseenkova-Bell, Marcin Golczak
The esterification of alcohols with fatty acids is a universal mechanism to form inert storage forms of sterols, di- and triacylglycerols, and retinoids. In ocular tissues, formation of retinyl esters is an essential step in the enzymatic regeneration of the visual chromophore (11-cis-retinal). Acyl-CoA wax alcohol acyltransferase 2 (AWAT2), also known as multifunctional O-acyltransferase (MFAT), is an integral membrane enzyme with a broad substrate specificity that has been shown to preferentially esterify 11-cis-retinol and thus contribute to formation of readily available pool of cis retinoids in the eye...
January 17, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28088325/molecular-dynamics-simulations-of-ternary-lipid-bilayers-containing-plant-sterol-and-glucosylceramide
#17
Shiva Emami, Sodeif Azadmard-Damirchi, Seyed Hadi Peighambardoust, Javad Hesari, Hadi Valizadeh, Roland Faller
An atomic-level molecular dynamics simulation was carried out to study the effects of a plant sterol (sitosterol) and glucosylceramide (GlcCer) on a 1,2-dilinoleoylposphocholine (DLiPC) membrane. Initially, a membrane containing 50mol% sitosterol was compared with that containing the same ratio of cholesterol. These simulations showed differential condensing and ordering effects of sitosterol and cholesterol, with cholesterol being slightly more efficient than sitosterol in packing the membrane more tightly to a liquid ordered phase...
January 11, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28077646/adenovirus-modulates-toll-like-receptor-4-signaling-by-reprogramming-orp1l-vap-protein-contacts-for-cholesterol-transport-from-endosomes-to-the-endoplasmic-reticulum
#18
Nicholas L Cianciola, Stacey Chung, Danny Manor, Cathleen R Carlin
: Human adenoviruses generally cause mild self-limiting infections but can lead to serious disease and even be fatal in high-risk individuals, underscoring the importance of understanding how the virus counteracts host defense mechanisms. This study had two goals. First, determine the molecular basis of cholesterol homeostatic responses induced by the early region 3 membrane protein RIDα via its direct interaction with the sterol-binding protein ORP1L. Second, determine how this interaction regulates innate immunity to adenovirus...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28071910/direct-measurement-of-the-effect-of-cholesterol-and-6-ketocholestanol-on-membrane-dipole-field-using-vibrational-stark-effect-spectroscopy-coupled-with-molecular-dynamics-simulations
#19
Rebika Shrestha, Cari M Anderson, Alfredo E Cardenas, Ron Elber, Lauren J Webb
Biological membranes are heterogeneous structures with complex electrostatic profiles arising from lipids, sterols, membrane proteins, and water molecules. We investigated the effect of cholesterol and its derivative 6-ketocholestanol (6-kc) on membrane electrostatics by directly measuring the dipole electric field (F ) within lipid bilayers containing cholesterol or 6-kc at concentrations of 0-40 mol% through the vibrational Stark effect (VSE). We found that adding low concentrations of cholesterol, up to ~10 mol%, increases F, while adding more cholesterol up to 40 mol% lowers F...
January 10, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28067450/lipid-raft-formation-key-role-of-polyunsaturated-phospholipids
#20
Chang Wang, Yuming Yu, Steven L Regen
The forces that drive lipid raft formation are poorly understood. To date, most of the attention has focused on attractive interactions between cholesterol and high-melting lipids. Remarkably little attention has been paid to repulsive forces. Here, we show that repulsive interactions between an exchangeable mimic of cholesterol and an exchangeable mimic of a low-melting phospholipid in liquid-disordered bilayers can be much stronger than the attractive forces between this same sterol and an exchangeable mimic of a high-melting phospholipid in liquid-ordered bilayers...
January 9, 2017: Angewandte Chemie
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