Background: Alopecia areata (AA) is a T-cell-mediated autoimmune disease that significantly impacts patient quality of life. The breakdown of hair follicle immune privilege underlies AA pathogenesis. However, the precise mechanism of this breakdown remains unclear.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2024
Many enveloped viruses bud from the plasma membrane that is tightly associated with a dense and thick actin cortex. This actin network represents a significant challenge for membrane deformation and scission, and how it is remodeled during the late steps of the viral cycle is largely unknown. Using superresolution microscopy, we show that HIV-1 buds in areas of the plasma membrane with low cortical F-actin levels.
View Article and Find Full Text PDFCell division is completed by the abscission of the intercellular bridge connecting the daughter cells. Abscission requires the polymerization of an ESCRT-III cone close to the midbody to both recruit the microtubule severing enzyme spastin and scission the plasma membrane. Here, we found that the microtubule and the membrane cuts are two separate events that are regulated differently.
View Article and Find Full Text PDFThe human immunodeficiency virus type 1 (HIV-1) is an intracellular pathogen whose replication cycle strictly depends on the host cell molecular machinery. HIV-1 crosses twice the plasma membrane, to get in and to get out of the cell. Therefore, the first and the last line of intracellular component encountered by the virus is the cortical actin network.
View Article and Find Full Text PDFActin is among the most abundant proteins in eukaryotic cells and assembles into dynamic filamentous networks regulated by many actin binding proteins. The actin cytoskeleton must be finely tuned, both in space and time, to fulfill key cellular functions such as cell division, cell shape changes, phagocytosis and cell migration. While actin oxidation by reactive oxygen species (ROS) at non-physiological levels are known for long to impact on actin polymerization and on the cellular actin cytoskeleton, growing evidence shows that direct and reversible oxidation/reduction of specific actin amino acids plays an important and physiological role in regulating the actin cytoskeleton.
View Article and Find Full Text PDFBroadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope glycoprotein (Env) are promising molecules for therapeutic or prophylactic interventions. Beyond neutralization, bNAbs exert Fc-dependent functions including antibody-dependent cellular cytotoxicity and activation of the complement. Here, we show that a subset of bNAbs targeting the CD4 binding site and the V1/V2 or V3 loops inhibit viral release from infected cells.
View Article and Find Full Text PDFThe midbody at the center of the intercellular bridge connecting dividing cells recruits the machinery essential for the final steps of cytokinesis. Successive abscission on both sides of the midbody generates a free midbody remnant (MBR) that can be inherited and accumulated in many cancer, immortalized, and stem cells, both in culture and in vivo. Strikingly, this organelle was recently shown to contain information that induces cancer cell proliferation, influences cell polarity, and promotes dorso-ventral axis specification upon interaction with recipient cells.
View Article and Find Full Text PDFProteins of the ADF/cofilin family play a central role in the disassembly of actin filaments, and their activity must be tightly regulated in cells. Recently, the oxidation of actin filaments by the enzyme MICAL1 was found to amplify the severing action of cofilin through unclear mechanisms. Using single filament experiments in vitro, we found that actin filament oxidation by MICAL1 increases, by several orders of magnitude, both cofilin binding and severing rates, explaining the dramatic synergy between oxidation and cofilin for filament disassembly.
View Article and Find Full Text PDFCytokinesis requires the constriction of ESCRT-III filaments on the side of the midbody, where abscission occurs. After ESCRT recruitment at the midbody, it is not known how the ESCRT-III machinery localizes to the abscission site. To reveal actors involved in abscission, we obtained the proteome of intact, post-abscission midbodies (Flemmingsome) and identified 489 proteins enriched in this organelle.
View Article and Find Full Text PDFCells don't simply separate at cytokinesis. While furrow contraction critically relies on myosin-II and F-actin, post-furrowing steps are less understood but involve the constriction of ESCRT-III polymer-dependent helices on the side of the midbody, which likely drive final abscission. The first evidence that animal cell cytokinesis requires membrane traffic, as in plant cells, was provided about 15 years ago.
View Article and Find Full Text PDFCytokinetic abscission is the terminal step of cell division, leading to the physical separation of the two daughter cells. The exact mechanism mediating the final scission of the intercellular bridge connecting the dividing cells is not fully understood, but requires the local constriction of endosomal sorting complex required for transport (ESCRT)-III-dependent helices, as well as remodelling of lipids and the cytoskeleton at the site of abscission. In particular, microtubules and actin filaments must be locally disassembled for successful abscission.
View Article and Find Full Text PDFCytokinetic abscission, the terminal step of cell division, crucially depends on the local constriction of ESCRT-III helices after cytoskeleton disassembly. While the microtubules of the intercellular bridge are cut by the ESCRT-associated enzyme Spastin, the mechanism that clears F-actin at the abscission site is unknown. Here we show that oxidation-mediated depolymerization of actin by the redox enzyme MICAL1 is key for ESCRT-III recruitment and successful abscission.
View Article and Find Full Text PDFMethods Cell Biol
August 2017
Cytokinesis is an essential step of cell proliferation leading to the physical separation of the dividing cells. Cytokinesis relies on both large scale and local scale cell shape changes, and terminates with the final abscission cut that requires close apposition of the plasma membrane. While furrow ingression is a prominent feature of the early phase of cytokinesis and is easy to visualize in all models, from dividing eggs to culture cells, the later steps of cytokinesis until abscission can be much more difficult to visualize.
View Article and Find Full Text PDFBST2 (bone marrow stromal antigen 2)/tetherin is a restriction factor of enveloped viruses, which blocks the release of viral particles. HIV-1 encodes proteins that antagonize this innate barrier, including the accessory protein Vpu. Here, we investigate whether the autophagy pathway and/or ATG proteins are hijacked by HIV-1 Vpu to circumvent BST2 restriction of viral release.
View Article and Find Full Text PDFThe functions of Beclin-1 in macroautophagy, tumorigenesis and cytokinesis are thought to be mediated by its association with the PI3K-III complex. Here, we describe a new role for Beclin-1 in mitotic chromosome congression that is independent of the PI3K-III complex and its role in autophagy. Beclin-1 depletion in HeLa cells leads to a significant reduction of the outer kinetochore proteins CENP-E, CENP-F and ZW10, and, consequently, the cells present severe problems in chromosome congression.
View Article and Find Full Text PDFEur Ann Allergy Clin Immunol
June 2010
Background: Foods containing flaxseed proteins rich inpolyunsaturatedfatty acids are new on the market.
Objectives: In a population of patients attending the allergology department, we evaluated the frequency of sensitization to flaxseed, characterized allergens and looked for modifications related to industrial processing.
Methods: Natural, heated and extruded flaxseeds were tested using prick-in-prick tests (PIP using the fresh seed), SDS PAGE, immunoblots, immunoblot inhibition and Fourier Transform Infrared (FTIR) spectroscopy.
The triggering receptor expressed on myeloid cells (TREM) 1, a receptor expressed on the surface of neutrophils and monocytes/macrophages, synergizes with the Toll-like receptors in amplifying the inflammatory response mediated by microbial components. Because the pathogenesis of severe blood loss-induced excessive inflammation and multiple organ failure implies leukocyte activation and bacterial translocation, we hypothesized that the TREM-1 pathway modulation would prove beneficial in this setting. Wistar rats were subjected to a 1-h period of hemorrhagic shock and then reperfused with shed blood and ringer lactate for 1 h.
View Article and Find Full Text PDFThe specific effects of heat treatment and/or addition of low/high-methylated pectin (LMP/HMP) on the allergenicity of beta-lactoglobulin (beta-Lg) and its hydrolysis products were investigated through a two-step in vitro digestion approach. beta-Lg was first hydrolyzed by pepsin and then by a trypsin/chymotrypsin (T/C) mixture done in a dialysis bag with a molecular weight cutoff of 1000. The protein digestion was followed by SDS-PAGE electrophoresis performed on each digestion product, and their in vitro allergenicity was analyzed by immunoblotting.
View Article and Find Full Text PDFThe aggregation of high-affinity IgE receptors (FcepsilonRI) on mast cells and basophils has long been known as the critical event that initiates allergic reactions. Monomeric IgE was recently found to induce a variety of effects when binding to FcepsilonRI. Upregulation of FcepsilonRI only requires binding, whereas other responses require FcepsilonRI aggregation.
View Article and Find Full Text PDFClin Exp Allergy
September 2004
Background: Peanut is a major allergenic product. Manufacturing processes used in food industries to improve the physicochemical properties of food-based peanut (stabilization, texturization), could cause a modification of the digestibility of peanut proteins and, consequently, their allergenicity.
Objective: This study aimed at examining the influence of polysaccharides, i.
Eur Ann Allergy Clin Immunol
March 2004
The most widely used ingredients in food formulation are proteins, lipids and polysaccharides. Proteins-lipids and proteins-polysaccharides interactions play a key role in the structure, stability, sensorial and nutritional properties of formulated foods. The objective of the present study is to highlight the importance of proteins-lipids and proteins-polysaccharides interactions, on the immuno-reactivity of allergenic proteins.
View Article and Find Full Text PDFRev Med Interne
February 2004
Introduction: Homocystinuria due to cystathionine beta synthase (CBS) deficiency is a special type of hyperhomocysteinemia because of its clinical expression (thrombotic events, ectopic lens and mental retardation). It's a rare, hereditary recessive autosomic disease generally diagnosed during childhood.
Exegesis: Thrombophilia examination in a 50-year-old man found a dramatically increase homocysteinemia.
Plant hydrocolloids used in the food industry to improve texture and stability of food, such as dairy products, can reduce protein digestibility and, consequently, modify the bioavailability of amino acids. We studied the in vitro hydrolysis at 37 degrees C of beta-lactoglobulin (beta-lg) in mixed dispersions containing either gum arabic or low-methylated pectin or xylan at levels of 0, 1, 10, 20, 30, and 50% weight. Proteolysis used either pepsin alone by progressive reduction of pH during proteolysis or pepsin followed by trypsin and chymotrypsin in two different dialysis bags with a molecular weight (MW) cutoff of 1000 or 8000 Da.
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