Emerging role of the scaffolding protein Dlg1 in interfacing with the vesicle trafficking machinery.: Dlg1 in the vesicle trafficking machinery

International audienceDiscs large 1 (Dlg1) is a modular scaffolding protein implicated in the control of cell polarity through assembly of specific multiprotein complexes, including receptors, ion channels and signaling proteins, at specialized zones of the plasma membrane. Recent data have shown that in addition to these well-known interaction partners, Dlg1 may also recruit components of the vesicle trafficking machinery either to the plasma membrane or to transport vesicles. Here, we discuss Dlg1 function in vesicle formation, targeting, tethering and fusion, in both the exocytotic and endocytotic pathways. These pathways contribute to cell functions as major and diverse as glutamatergic activity in the neurons, membrane homeostasis in Schwann cell myelination, insulin stimulation of glucose transport in adipocytes, or endothelial secretion of the hemostatic protein, von Willebrand factor (VWF)

Rôle de la protéine "Disc Large" dans les cellules de la paroi vasculaire humaine

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Fatty acid metabolism meets organelle dynamics.

International audienceUpon nutrient deprivation, cells metabolize fatty acids (FAs) in mitochondria to supply energy, but how FAs, stored as triacylglycerols in lipid droplets, reach mitochondria has been mysterious. Rambold et al. (2015) now show that FA mobilization depends on triacylglycerol lipolysis, whereas autophagy feeds the lipid droplet pool for continued fueling of mitochondria

Prostaglandin (PG) FP and EP\u3csub\u3e1\u3c/sub\u3e receptors mediate PGF\u3csub\u3e2α\u3c/sub\u3e and PGE\u3csub\u3e2\u3c/sub\u3e regulation of interleukin-1β expression in Leydig cell progenitors

Prostaglandins (PG) mediate IL-1β regulation of several interleukin mRNAs in progenitor Leydig cells. PGE2 and PGF2α potently reverse indomethacin (INDO; a cyclooxygenase inhibitor) inhibition of IL-1β autoinduction. IL-1β increases PGE2 and PGF2α production. To determine the PG receptors involved in this regulation, this study established by RT-PCR and Western analyses which specific receptors for PGE2 (EP receptors) and PGF2α (FP receptors) are expressed in progenitors. Pharmacological characterization of receptors involved in PGE2 and PGF2α regulation of IL-1β mRNA levels was ascertained using real-time PCR analyses. FP, EP1, EP2, and EP4 receptor mRNAs and proteins, and an EP3 receptor subtype were detected. IL-1β treatment (24-h) significantly decreased EP1 receptor levels; INDO abrogated this down-regulation. FP, EP2, and EP4 receptor levels increased after IL-1β and IL-1β + INDO. A selective FP agonist, cloprostenol (0.1 μM), and PGF2α (10 μM) had similar effects on IL-1β mRNA levels in progenitors treated with IL-1β + INDO. None of the EP2/EP4 agonists [butaprost, misoprostol, or 11-deoxy PGEx (10 μM)] affected IL-1β mRNA levels. In contrast, EP1/EP3 agonists (17-phenyl trinor PGE2 and sulprostone) increased IL-1β mRNAs in a dose-dependent manner. EP1 receptor subtype-selective antagonist, SC-51322, blocked IL-1β-induced and [IL-1β + INDO + 17-phenyl trinor PGE2]-induced increases in IL-1β mRNAs. Taken together, our data demonstrate that FP and EP1 receptors mediate PGF2α and PGE2 induction of progenitor IL-1β expression

Lipids and Their Trafficking: An Integral Part of Cellular Organization.

International audienceAn evolutionarily conserved feature of cellular organelles is the distinct phospholipid composition of their bounding membranes, which is essential to their identity and function. Within eukaryotic cells, two major lipid territories can be discerned, one centered on the endoplasmic reticulum and characterized by membranes with lipid packing defects, the other comprising plasma-membrane-derived organelles and characterized by membrane charge. We discuss how this cellular lipid organization is maintained, how lipid flux is regulated, and how perturbations in cellular lipid homeostasis can lead to disease

Discs large 1 (Dlg1) scaffolding protein participates with clathrin and adaptator protein complex 1 (AP-1) in forming Weibel-Palade bodies of endothelial cells.

International audienceWeibel-Palade bodies (WPBs) are specific cigar-shaped granules that store von Willebrand factor (VWF) for its regulated secretion by endothelial cells. The first steps of the formation of these granules at the trans-Golgi network (TGN) specifically require VWF aggregation and an external scaffolding complex that contains the adaptator protein complex 1 (AP-1) and clathrin. Discs large 1 (Dlg1) is generally considered to be a modular scaffolding protein implicated in the control of cell polarity in a large variety of cells by specific recruiting of receptors, channels or signaling proteins to specialized zones of the plasma membrane. We propose here that in endothelial cells, Dlg1 in a complex with AP-1 and clathrin participates in the biogenesis of WPBs. Supporting data show that Dlg1 colocalizes with microtubules, intermediate filaments and Golgi markers. Tandem mass spectrometry experiments led to the identification of clathrin as a Dlg1-interacting partner, interaction was confirmed by in situ proximity ligation assays. Furthermore, AP-1 and VWF immunoprecipitate and colocalize with Dlg1 in the juxta-nuclear zone. Finally, Dlg1 depletion by siRNA duplexes disrupts TGN morphology and WPB formation. Our results provide the first evidence for an unexpected role of Dlg1 in controlling the formation of specific secretory granules involved in VWF exocytosis in endothelial cells

Metabarcoding reveals waterbird diet in a French Ramsar wetland: implications for ecosystem management

International audienceEnvironmental and/or climate changes, occurring at a global or local scale, can significantly impact the diets, health, and population dynamics of waterbirds. This study aimed to develop an effective tool, using DNA metabarcoding of fecal samples, for monitoring waterbird diets during the breeding season in a Ramsar freshwater wetland in Northern France. We collected bird feces across eight marshes with varying anthropic usage. The majority of samples (69%) were from five waterbird species: Eurasian coot ( Fulica atra ), Eurasian moorhen ( Gallinula chloropus ), mallard ( Anas platyrhynchos ), mute swan ( Cygnus olor ), and grey heron ( Ardea cinerea ). DNA was extracted from 116 samples, with plant and invertebrate primers used to undertake multi-marker metabarcoding. Despite a negative impact of uric acid on DNA amplification, we observed significant dietary variations among bird species and sampling sites. Wetland bird diets primarily consisted of four arthropod families, dominated by Chironomidae and Asellidae. The number of plant families detected was higher, consisting of 33 families, with Poaceae highly prevalent within wetland bird diets. This study shows that using DNA metabarcoding to explore interactions between waterbirds and trophic resources is a promising approach to assist wetland management and assess the effect of environmental changes