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Ken Hsu and Caroline Franks discuss new diacylglycerol kinase research

Ken Hsu, Assistant Professor of Chemistry at the University of Virginia, and Caroline Franks, a graduate student at the Hsu Lab, discuss their research on diacylglycerol kinases (DGKs). Franks is the first author on the paper, "The Ligand Binding Landscape of Diacylglycerol Kinases," which was published in Cell Chemical Biology. Access the abstract here: http://bit.ly/2vSIJQU.

  

Nicolas G. Bazan, LSUHSC School of Medicine

The recent discovery of elovanoids are novel cell-specific lipid mediators necessary for neuroprotective signaling for photoreceptor cell integrity.

 

Understanding phospholipid function: Why are there so many lipids?

Bill Dowhan has beautifully described in this expansive commentary both the personal details of the arc of his career, but also an encapsulation of how the study of lipids has progressed from that annoying grease that was disposed of while purifying proteins to the study of the function of the dazzling array of lipids that cells depend on. This is an inspiring must-read for lipidologists at all stages of their careers by one of the true greats in lipid research.

Dr. Dowhan explains this scientific evolution in a video that can be found here.

 

Cryo-EM structure and biochemical analysis reveal the basis of the functional difference between human PI3KC3-C1 and -C2

Phosphatidylinositol-3-kinases are well-recognized signaling enzymes involved in a number of physiological and pathophysiological pathways. Two isoforms that differ in a specific region are studied in this report using cryo-EM and biochemical analyses to reveal functional differences. The authors show suggest their results indicate that structural elements that dictate different lipid binding capacity is central to the different functions of these isozymes.

 

Friction Mediates Scission of Tubular Membranes Scaffolded by BAR Proteins

We are used to there being a friction between the lipid world and the protein world, but little did we know that this friction is an important component of membrane remodeling. The French groups of Patricia Bassereau and Andrew Callan-Jones report that the dynamin-independent scission of endocytic vesicles is driven by the friction generated by the interaction of lipids and BAR-domain proteins.

 

The phospholipase iPLA2γ is a major mediator releasing oxidized aliphatic chains from cardiolipin, integrating mitochondrial bioenergetics and signaling.

April 25, 2017

Liu et al. investigated the role of the calcium-independent phospholipase A2γ (iPLA2γ) in the hydrolysis of cardiolipin (CL), a phospholipid that plays a role in mitochondrial bioenergetics and signaling.

 

Introducing inducible fluorescent split cholesterol oxidase to mammalian cells

May 26, 2017

Chernov et al. developed a recombinant cholesterol oxidase linked to GFP that was inducible by rapamycin that can serve as a tool for modulating cholesterol levels in mammalian cells. The fluorescence of this recombinant enzyme correlates to its oxidation activity. Upon rapamycin removal, the enzyme loses both florescence and oxidation activity.

 

Switching head group selectivity in mammalian sphingolipid biosynthesis by active-site-engineering of sphingomyelin synthases

May 10, 2016

Kol et al. identified a single residue in the active site of sphingomyelin synthase (SMS) that greatly influences enzyme specificity. By swapping this one amino acid from aspartic acid to glutamic acid the researchers were able to turn an SMS into a ceramide phosphoethanolamine synthase.

 

Direct quantitative determination of ceramide glycosylation in vivo: a new approach to evaluate cellular enzyme activity of glucosylceramide synthase

October 13, 2010

Yong-Y Liu and colleagues have optimized a rapid and facile HPLC method for measuring glucosylceramide synthase activity in cells, tissues, and the intact animal. Glucosylceramide synthase initiates the synthesis of glycosphingolipids. Its activity is a target for Gaucher’s disease but decreased activity is also implicated in ceramide-induced toxicity. The ability to rapidly and easily measure glucosylceramide synthase activity is an important addition to our tools to gauge the consequences of increased and decreased levels of activity of this key sphingolipid metabolic enzyme.

 

Video: Kyle Korshavn at the University of Michigan

June 16, 2017

Kyle Korshavn is a postdoc in Ayyalusamy Ramamoorthy's lab at the University of Michigan. In this video, he describes the research presented recently in the Journal of Biological Chemistry paper: Reduced Lipid Bilayer Thickness Regulates the Aggregation and Cytotoxicity of Amyloid-β.

To read the Journal of Biological Chemistry abstract: http://bit.ly/2sy25Kn

 

Video: Bad cholesterol carrier: visualization technique reveals unusual shape

June 13, 2017

Researchers at Lawrence Berkeley Research Laboratory and Children’s Hospital Oakland Research Institute have developed a new 3-D technique called individual particle electron tomography (IPET), allowing them to visualize the carriers of cholesterol. Their research has revealed a unique polyhedral shape to very low-density lipoproteins (VLDL), implicated in the development of cardiovascular disease. This discovery in shape can direct future studies into how flat faces and sharp edges of these molecules affect cholesterol transport and lead to disease.

To read the JLR manuscript “Polyhedral 3D Structure of Human Plasma Very-Low-Density Lipoproteins by Individual Particle Cryo-Electron Tomography,” please visit http://www.jlr.org/content/57/10/1879.

Video: https://www.youtube.com/watch?v=EXSCUppzVUo

 

Adductome-based identification of biomarkers for lipid peroxidation

May 19, 2017

Takahiro Shibata, Kazuma Shimizu, Keita Hirano, Fumie Nakashima, Ryosuke Kikuchi, Tadashi Matsushita, and Koji Uchida

Lipid peroxidation is an endogenous source of aldehydes that gives rise to covalent modification of proteins in various pathophysiological states. In this study, a strategy for the comprehensive detection and comparison of adducts was applied to find a biomarker for lipid peroxidation-modified proteins in vivo.

 

ApoE and Lipid Homeostasis in Alzheimer’s Disease: Introduction to the Thematic Review Series

May 2017

Ta-Yuan Chang and Catherine Chang

The pathological hallmarks of AD involve amyloidopathy, taupathy, and chronic neuroinflammation. AD can be classified as early onset (EOAD) and late onset (LOAD), with 99% of the cases being LOAD. EOAD occurs in young adults and is usually caused by rare mutations of genes directly involved in processing of the amyloid precursor protein.

 

Aromatic residues in the C terminus of apolipoprotein C-III mediate lipid binding and LPL inhibition

May 2017

Nathan L. Meyers, Mikael Larsson, Evelina Vorrsjö, Gunilla Olivecrona, and Donald M. Small

ApoC-III elevates TG in part by inhibiting LPL. ApoC-III likely inhibits LPL by competing for lipid binding. To probe this, we used oil-drop tensiometry to characterize binding of six apoC-III variants to lipid/water interfaces.

 

Lipid sensing by mTOR complexes via de novo synthesis of phosphatidic acid

April 2017

Deepak Menon, Darin Salloum, Elyssa Bernfeld, Elizabeth Gorodetsky, Alla Akselrod, Maria A. Frias, Jessica Sudderth, Pei-Hsuan Chen, Ralph DeBerardinis and David A. Foster

We report here that mTORC1 and mTORC2 are activated in response to exogenously supplied fatty acids via the de novo synthesis of PA, a central metabolite for membrane phospholipid biosynthesis. We examined the impact of exogenously supplied fatty acids on mTOR in KRas-driven cancer cells, which are programmed to utilize exogenous lipids.

 

PI-PLC β1 in differentiation and disease

March 1, 2017

Lucio Cocco

Evidence from several laboratories has highlighted the presence of autonomous nuclear inositol lipid metabolism. The evidence suggests that lipid molecules are important components of signaling pathways operating within the nucleus. The findings are important, given the fact that nuclear signaling activity controls cell growth and differentiation.

 

Proteins and lipids — a complicated relationship?

January 5, 2017

Eva Sevcsik & Gerhard J. Schütz

Researchers have been discussing for many years the role of the lipid matrix in regulating the activity and the organization of membrane proteins. A variety of effects have been singled out and studied qualitatively and quantitatively in model systems. However, the applicability of those results to living cells is — in many cases — unsatisfactory. Here, we would like to make the point that the complexity of the lipid–protein matrix in cells alters the physico-chemical mechanisms of protein–lipid interactions to an unknown extent when compared to model systems.

 

 

  
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