Anionic lipids enriched at the ExPortal of Streptococcus pyogenes

The ExPortal of Streptococcus pyogenes is a membrane microdomain dedicated to the secretion and folding of proteins. We investigated the lipid composition of the ExPortal by examining the distribution of anionic membrane phospholipids. Staining with 10-N-nonyl-acridine orange revealed a single microdomain enriched with an anionic phospholipid whose staining characteristics and behavior in a cardiolipin-deficient mutant were characteristic of phosphatidylglycerol. Furthermore, the location of the microdomain corresponded to the site of active protein secretion at the ExPortal. These results indicate that the ExPortal is an asymmetric lipid microdomain, whose enriched content of anionic phospholipids may play an important role in ExPortal organization and protein trafficking.     

GPIHBP1: an endothelial cell molecule important for the lipolytic processing of chylomicrons

PURPOSE OF REVIEW: To summarize recent data indicating that glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) plays a key role in the lipolytic processing of chylomicrons. RECENT FINDINGS: Lipoprotein lipase hydrolyses triglycerides in chylomicrons at the luminal surface of the capillaries in heart, adipose tissue, and skeletal muscle. The endothelial cell molecule that facilitates the lipolytic processing of chylomicrons has never been clearly defined. Mice lacking GPIHBP1 manifest chylomicronemia, with plasma triglyceride levels as high as 5000 mg/dl. In wild-type mice, GPIHBP1 is expressed on the luminal surface of capillaries in heart, adipose tissue, and skeletal muscle. Cells transfected with GPIHBP1 bind both chylomicrons and lipoprotein lipase avidly. SUMMARY: The chylomicronemia in Gpihbp1-deficient mice, the fact that GPIHBP1 is located within the lumen of capillaries, and the fact that GPIHBP1 binds lipoprotein lipase and chylomicrons suggest that GPIHBP1 is a key platform for the lipolytic processing of triglyceride-rich lipoproteins.     

Radiation of the Tnt1 retrotransposon superfamily in three Solanaceae genera

Background  

Tnt1 was the first active plant retrotransposon identified in tobacco after nitrate reductase gene disruption. The Tnt1 superfamily comprises elements from Nicotiana (Tnt1 and Tto1) and Lycopersicon (Retrolyc1 and Tlc1) species. The study presented here was conducted to characterise Tnt1-related sequences in 20 wild species of Solanum and five cultivars of Solanum tuberosum.     

Identification of proteins involved in microglial endocytosis of alpha-synuclein

Aggregated alpha-synuclein, a protein playing pivotal roles in the pathogenesis of Parkinson disease (PD) and related synucleinopathy, has been shown to activate microglia, the key cells in neuroinflammation. However, the mechanisms by which aggregated alpha-synuclein enters microglia remain uncharacterized. In this study, we first replicated our previous results with a modified protocol that generated aggregated alpha-synuclein more efficiently. Next, using two recently developed proteomic techniques, SILAC (Stable Isotope Labeling of Amino acid in Cell cultures) and PROCEED (PROteome of Cell Exposed Extracellular Domains), we studied the plasma membrane proteins of primary cultured microglia that might be interacting with aggregated alpha-synuclein and mediating its internalization. The results demonstrated that 250 nM alpha-synuclein, aged for 6 h with a magnetic stir bar, was just as potent in activating microglia as the aggregated alpha-synuclein produced by aging without constant agitation for 7 days. The proteomic analysis identified 111 membrane proteins; of these, 46 proteins were altered in relative abundance in the membrane compartment after treatment with aggregated alpha-synuclein for 3 h. Two of these proteins, clathrin and calnexin, were further evaluated with Western blotting, demonstrating good agreement with quantitative proteomics. Finally, immunocytochemical as well as co-immunoprecipitation studies indicated that clathrin was indeed co-localized with internalized alpha-synuclein in microglia. These results suggest for the first time that microglial activation secondary to internalization of aggregated alpha-synuclein likely requires participation of clathrin, which is an essential protein of the polyhedral coat of coated pits and vesicles that play major roles in endocytosis and vesicular trafficking.     

Discovery of a piperazine urea based compound as a potent, selective, orally bioavailable melanocortin subtype-4 receptor partial agonist

We report the discovery of piperazine urea based compound 1, a potent, selective, orally bioavailable melanocortin subtype-4 receptor partial agonist. Compound 1 shows anti-obesity efficacy without potentiating erectile activity in the rodent models.     

Applications of systems biology towards microbial fuel production

Harnessing the immense natural diversity of biological functions for economical production of fuel has enormous potential benefits. Inevitably, however, the native capabilities for any given organism must be modified to increase the productivity or efficiency of a biofuel bioprocess. From a broad perspective, the challenge is to sufficiently understand the details of cellular functionality to be able to prospectively predict and modify the cellular function of a microorganism. Recent advances in experimental and computational systems biology approaches can be used to better understand cellular level function and guide future experiments. With pressure to quickly develop viable, renewable biofuel processes a balance must be maintained between obtaining depth of biological knowledge and applying that knowledge.