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Plasma membrane ceramide

Lelin Hu, Hao Wang, Li Huang, Yong Zhao, Junjie Wang
Autophagy induced by radiation is critical to cell fate decision. Evidence now sheds light on the importance of autophagy induced by cancer radiotherapy. Traditional view considers radiation can directly or indirectly damage DNA which can activate DNA damage the repair signaling pathway, a large number of proteins participating in DNA damage repair signaling pathway such as p53, ATM, PARP1, FOXO3a, mTOR and SIRT1 involved in autophagy regulation. However, emerging recent evidence suggests radiation can also cause injury to extranuclear targets such as plasma membrane, mitochondria and endoplasmic reticulum (ER) and induce accumulation of ceramide, ROS, and Ca2+ concentration which activate many signaling pathways to modulate autophagy...
October 5, 2016: International Journal of Oncology
Birol Cabukusta, Jan A Köhlen, Christian P Richter, Changjiang You, Joost C M Holthuis
Single-molecule photobleaching has emerged as a powerful non-invasive approach to extract the stoichiometry of multimeric membrane proteins in their native cellular environment. However, this method has mainly been used to determine the subunit composition of ion channels and receptors at the plasma membrane. In here we applied single-molecule photobleaching to analyse the oligomeric state of an ER-resident candidate ceramide sensor protein, SMSr/SAMD8. Co-immunoprecipitation and chemical crosslinking studies previously revealed that the N-terminal sterile alpha motif or SAM domain of SMSr drives self-assembly of the protein into oligomers and that SMSr oligomerization is promoted by curcumin, a drug known to perturb ER ceramide and calcium homeostasis...
October 10, 2016: Journal of Biological Chemistry
Virginia Tartaglio, Emilie A Rennie, Rebecca Cahoon, George Wang, Edward Baidoo, Jennifer C Mortimer, Edgar B Cahoon, Henrik V Scheller
Sphingolipids are a major component of plant plasma membranes and endomembranes, and mediate a diverse range of biological processes. Study of the highly glycosylated glycosyl inositol phosphorylceramide (GIPC) sphingolipids, has been slow due to challenges associated with GIPCs' extractability, and their functions in the plant remain poorly characterized. We recently discovered an Arabidopsis GIPC glucuronosyltransferase, INOSITOL PHOSPHORYLCERAMIDE GLUCURONOSYLTRANSFERASE 1 (IPUT1), which is the first enzyme in the GIPC glycosylation pathway...
September 19, 2016: Plant Journal: for Cell and Molecular Biology
Ruo-Xu Gu, Helgi I Ingólfsson, Alex H de Vries, Siewert J Marrink, D Peter Tieleman
Gangliosides are glycolipids in which an oligosaccharide headgroup containing one or more sialic acids is connected to a ceramide. Gangliosides reside in the outer leaflet of the plasma membrane and play a crucial role in various physiological processes such as cell signal transduction and neuronal differentiation by modulating structures and functions of membrane proteins. Because the detailed behavior of gangliosides and protein-ganglioside interactions are poorly known, we investigated the interactions between the gangliosides GM1 and GM3 and the proteins aquaporin (AQP1) and WALP23 using equilibrium molecular dynamics simulations and potential of mean force calculations at both coarse-grained (CG) and atomistic levels...
October 4, 2016: Journal of Physical Chemistry. B
Heidi A Neubauer, Duyen H Pham, Julia R Zebol, Paul A B Moretti, Amanda L Peterson, Tamara M Leclercq, Huasheng Chan, Jason A Powell, Melissa R Pitman, Michael S Samuel, Claudine S Bonder, Darren J Creek, Briony L Gliddon, Stuart M Pitson
While both human sphingosine kinases (SK1 and SK2) catalyze the generation of the pleiotropic signaling lipid sphingosine 1-phosphate, these enzymes appear to be functionally distinct. SK1 has well described roles in promoting cell survival, proliferation and neoplastic transformation. The roles of SK2, and its contribution to cancer, however, are much less clear. Some studies have suggested an anti-proliferative/pro-apoptotic function for SK2, while others indicate it has a pro-survival role and its inhibition can have anti-cancer effects...
August 30, 2016: Oncotarget
Leandro N Ventimiglia, Miguel A Alonso
Exosomes are a particular type of extracellular vesicle, characterized by their endosomal origin as intraluminal vesicles present in large endosomes with a multivesicular structure. After these endosomes fuse with the plasma membrane, exosomes are secreted into the extracellular space. The ability of exosomes to carry and selectively deliver bioactive molecules (e.g., lipids, proteins, and nucleic acids) confers on them the capacity to modulate the activity of receptor cells, even if these cells are located in distant tissues or organs...
2016: Frontiers in Cell and Developmental Biology
Yang Yu, Matej Skočaj, Mateja Erdani Kreft, Nataša Resnik, Peter Veranič, Pietro Franceschi, Kristina Sepčić, Graziano Guella
Comparative lipidomic studies were performed across the RT4 versus T24 urothelial cancer cell lines, as models for noninvasive urothelial papilloma cells (with a relatively high level of differentiation) and invasive urothelial carcinoma cells (with low level of differentiation), respectively. The aim was to investigate the differences in lipid profile associated with different levels of urothelial cancer cell invasiveness. The cellular lipidomes were characterized using our previously developed joint methodology of liquid chromatography-mass spectrometry and high-resolution nuclear magnetic resonance, which included analysis of the phospholipids and ceramide-based glycosphingolipids...
October 18, 2016: Molecular BioSystems
Rosi Bissinger, Elisabeth Lang, Mehrdad Ghashghaeinia, Yogesh Singh, Christine Zelenak, Birgit Fehrenbacher, Sabina Honisch, Hong Chen, Hajar Fakhri, Anja T Umbach, Guilai Liu, Rexhep Rexhepaj, Guoxing Liu, Martin Schaller, Andreas F Mack, Adrian Lupescu, Lutz Birnbaumer, Florian Lang, Syed M Qadri
Putative functions of the heterotrimeric G-protein subunit Gαi2-dependent signaling include ion channel regulation, cell differentiation, proliferation and apoptosis. Erythrocytes may, similar to apoptosis of nucleated cells, undergo eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) exposure. Eryptosis may be triggered by increased cytosolic Ca(2+) activity and ceramide. In the present study, we show that Gαi2 is expressed in both murine and human erythrocytes and further examined the survival of erythrocytes drawn from Gαi2-deficient mice (Gαi2(-/-)) and corresponding wild-type mice (Gαi2(+/+))...
2016: Scientific Reports
Aditi Chaudhari, Liliana Håversen, Reza Mobini, Linda Andersson, Marcus Ståhlman, Emma Lu, Mikael Rutberg, Per Fogelstrand, Kim Ekroos, Adil Mardinoglu, Malin Levin, Rosie Perkins, Jan Borén
Lipid droplet formation, which is driven by triglyceride synthesis, requires several droplet-associated proteins. We identified ARAP2 (an ADP-ribosylation factor 6 GTPase-activating protein) in the lipid droplet proteome of NIH-3T3 cells and showed that knockdown of ARAP2 resulted in decreased lipid droplet formation and triglyceride synthesis. We also showed that ARAP2 knockdown did not affect fatty acid uptake but reduced basal glucose uptake, total levels of the glucose transporter GLUT1, and GLUT1 levels in the plasma membrane and the lipid micro-domain fraction (a specialized plasma membrane domain enriched in sphingolipids)...
July 27, 2016: Biochimica et Biophysica Acta
N I Hanafi, A S Mohamed, J Md Noor, N Abdu, Hamid Hasani, R Siran, N J Osman, S Ab Rahim, S H Sheikh Abdul Kadir
Ursodeoxycholic acid (UDCA) is used to treat liver diseases and demonstrates cardioprotective effects. Accumulation of the plasma membrane sphingolipid sphingomyelin in the heart can lead to atherosclerosis and coronary artery disease. Sphingomyelinases (SMases) break down sphingomyelin, producing ceramide, and inhibition of SMases activity can promote cell survival. We hypothesized that UDCA regulates activation of ERK and Akt survival signaling pathways and SMases in protecting cardiac cells against hypoxia...
2016: Genetics and Molecular Research: GMR
Carolyn M Shirey, Katherine E Ward, Robert V Stahelin
Ceramide-1-phosphate (C1P) is an important signaling sphingolipid and a metabolite of ceramide. C1P contains an anionic phosphomonoester head group and has been shown to regulate physiological and pathophysiological processes such as cell proliferation, inflammation, apoptosis, phagocytosis, and macrophage chemotaxis. Despite this mechanistic information on its role in intra- and intercellular communication, little information is available on the biophysical properties of C1P in biological membranes and how it interacts with effector proteins...
June 15, 2016: Chemistry and Physics of Lipids
Chinmay Das, Peter D Olmsted
The stratum corneum (SC), the outermost layer of skin, comprises rigid corneocytes (keratin-filled dead cells) in a specialized lipid matrix. The continuous lipid matrix provides the main barrier against uncontrolled water loss and invasion of external pathogens. Unlike all other biological lipid membranes (such as intracellular organelles and plasma membranes), molecules in the SC lipid matrix show small hydrophilic groups and large variability in the length of the alkyl tails and in the numbers and positions of groups that are capable of forming hydrogen bonds...
July 28, 2016: Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences
Ronald L Schnaar
Gangliosides, sialylated glycosphingolipids, found on all vertebrate cells and tissues, are major molecular determinants on the surfaces of vertebrate nerve cells. Composed of a sialylated glycan attached to a ceramide lipid, the same four structures-GM1, GD1a, GD1b, and GT1b-represent the vast majority (>90%) of gangliosides in the brains of all mammals and birds. Primarily found on the outer surface of the plasma membrane with their glycans facing outward, gangliosides associate laterally with each other, sphingomyelin, cholesterol, and select proteins in lipid rafts-the dynamic functional subdomains of the plasma membrane...
August 14, 2016: Journal of Molecular Biology
Christopher E Gonzalez, Vijay K Venkatraman, Yang An, Bennett A Landman, Christos Davatzikos, Veera Venkata Ratnam Bandaru, Norman J Haughey, Luigi Ferrucci, Michelle M Mielke, Susan M Resnick
Sphingolipids serve important structural and functional roles in cellular membranes and myelin sheaths. Plasma sphingolipids have been shown to predict cognitive decline and Alzheimer's disease. However, the association between plasma sphingolipid levels and brain white matter (WM) microstructure has not been examined. We investigated whether plasma sphingolipids (ceramides and sphingomyelins) were associated with magnetic resonance imaging-based diffusion measures, fractional anisotropy (FA), and mean diffusivity, 10...
July 2016: Neurobiology of Aging
Rawad Abdayem, Florian Formanek, Anne Marie Minondo, Anne Potter, Marek Haftek
During the formation of the stratum corneum (SC) barrier, the extracellular spaces of viable epidermis, rich in glycans, are filled with a highly organized lipid matrix and the plasma membranes of keratinocytes are replaced by cornified-lipid envelopes. These structures comprise cross-linked proteins, including trans-membrane glycoproteins and proteoglycans, covalently bound to a monolayer of cell surface ceramides. Little is known about the presence and distribution of glycans on the SC corneocytes despite their possible involvement in SC hydration, cohesion and desquamation...
May 19, 2016: Experimental Dermatology
Matthijs Kol, Radhakrishnan Panatala, Mirjana Nordmann, Leoni Swart, Leonie van Suijlekom, Birol Cabukusta, Angelika Hilderink, Tanja Grabietz, John G M Mina, Pentti Somerharju, Sergei Korneev, Fikadu G Tafesse, Joost C M Holthuis
SM is a fundamental component of mammalian cell membranes that contributes to mechanical stability, signaling, and sorting. Its production involves the transfer of phosphocholine from phosphatidylcholine onto ceramide, a reaction catalyzed by SM synthase (SMS) 1 in the Golgi and SMS2 at the plasma membrane. Mammalian cells also synthesize trace amounts of the SM analog ceramide phosphoethanolamine (CPE), but the physiological relevance of CPE production is unclear. Previous work revealed that SMS2 is a bifunctional enzyme producing both SM and CPE, whereas a closely related enzyme, sphingomyelin synthase-related protein (SMSr)/SAMD8, acts as a monofunctional CPE synthase in the endoplasmatic reticulum...
July 2016: Journal of Lipid Research
M Tafelmeier, A Fischer, E Orsó, T Konovalova, A Böttcher, G Liebisch, S Matysik, G Schmitz
Stored platelet concentrates (PLCs) for therapeutic purpose, develop a platelet storage lesion (PSL), characterized by impaired platelet (PLT) viability and function, platelet extracellular vesicle (PL-EV) release and profound lipidomic changes. Whereas oxidized low-density lipoprotein (oxLDL) activates PLTs and promotes atherosclerosis, effects linked to oxidized high-density lipoprotein (oxHDL) are poorly characterized. PLCs from blood donors were treated with native (nHDL) or mildly oxidized HDL (moxHDL) for 5days under blood banking conditions...
May 6, 2016: Journal of Steroid Biochemistry and Molecular Biology
Julien Gronnier, Véronique Germain, Paul Gouguet, Jean-Luc Cacas, Sébastien Mongrand
What are the most abundant sphingolipids on earth? The answer is Glycosyl Inositol Phosphoryl Ceramides (GIPCs) present in fungi and the green lineage. In this review, we discuss the putative role of plant GIPCs in the lipid bilayer asymmetry, in the lateral organization of membrane rafts and in the very long chain fatty acid inter-leaflet coupling of lipids in the plant plasma membrane (PM). A special focus on the structural similarities -and putative functions- of GIPCs is discussed by comparison with animal gangliosides, structural homologs of plant GIPCs...
2016: Plant Signaling & Behavior
Elisabeth Corcelle-Termeau, Signe Diness Vindeløv, Saara Hämälistö, Baharia Mograbi, Anne Keldsbo, Jan Hinrich Bräsen, Elena Favaro, Dieter Adam, Piotr Szyniarowski, Paul Hofman, Stefan Krautwald, Thomas Farkas, Nikolaj H T Petersen, Mikkel Rohde, Andreas Linkermann, Marja Jäättelä
Sphingomyelin is an essential cellular lipid that traffics between plasma membrane and intracellular organelles until directed to lysosomes for SMPD1 (sphingomyelin phosphodiesterase 1)-mediated degradation. Inactivating mutations in the SMPD1 gene result in Niemann-Pick diseases type A and B characterized by sphingomyelin accumulation and severely disturbed tissue homeostasis. Here, we report that sphingomyelin overload disturbs the maturation and closure of autophagic membranes. Niemann-Pick type A patient fibroblasts and SMPD1-depleted cancer cells accumulate elongated and unclosed autophagic membranes as well as abnormally swollen autophagosomes in the absence of normal autophagosomes and autolysosomes...
May 3, 2016: Autophagy
Lena Collenburg, Tim Walter, Anne Burgert, Nora Müller, Jürgen Seibel, Lukasz Japtok, Burkhard Kleuser, Markus Sauer, Sibylle Schneider-Schaulies
Sphingolipids are major components of the plasma membrane. In particular, ceramide serves as an essential building hub for complex sphingolipids, but also as an organizer of membrane domains segregating receptors and signalosomes. Sphingomyelin breakdown as a result of sphingomyelinase activation after ligation of a variety of receptors is the predominant source of ceramides released at the plasma membrane. This especially applies to T lymphocytes where formation of ceramide-enriched membrane microdomains modulates TCR signaling...
May 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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