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Lipid raft

Diana Golden, Antonina Kolmakova, Sunitha Sura, Anthony T Vella, Ani Manichaikul, Xin-Qun Wang, Suzette J Bielinski, Kent D Taylor, Yii-Der Ida Chen, Stephen S Rich, Annabelle Rodriguez
BACKGROUND: The lipoprotein scavenger receptor BI (SCARB1) rs10846744 noncoding variant is significantly associated with atherosclerotic disease independently of traditional cardiovascular risk factors. We identified a potentially novel connection between rs10846744, the immune checkpoint inhibitor lymphocyte activation gene 3 (LAG3), and atherosclerosis. METHODS: In vitro approaches included flow cytometry, lipid raft isolation, phosphosignaling, cytokine measurements, and overexpressing and silencing LAG3 protein...
October 20, 2016: JCI Insight
Tamás Kovács, Gyula Batta, Tímea Hajdu, Ágnes Szabó, Tímea Váradi, Florina Zákány, István Csomós, János Szöllősi, Peter Nagy
Although activation of the ErbB family of receptor tyrosine kinases (ErbB1-4) is driven by oligomerization mediated by intermolecular interactions between the extracellular, the kinase and the transmembrane domains, the transmembrane domain has been largely neglected in this regard. The largest contributor to the intramembrane electric field, the dipole potential, alters the conformation of transmembrane peptides, but its effect on ErbB proteins is unknown. Here, we show by Förster resonance energy transfer (FRET) and number and brightness (N&B) experiments that the epidermal growth factor (EGF)-induced increase in the homoassociation of ErbB1 and ErbB2 and their heteroassociation are augmented by increasing the dipole potential...
October 24, 2016: Scientific Reports
Raquel Marin, Noemí Fabelo, Virginia Martín, Paula Garcia-Esparcia, Isidre Ferrer, David Quinto-Alemany, Mario Díaz
Lipid rafts are highly dynamic membrane microdomains intimately associated with cell signaling. Compelling evidence has demonstrated that alterations in lipid rafts are associated with neurodegenerative diseases such Alzheimer's disease, but at present, whether alterations in lipid raft microdomains occur in other types of dementia such dementia with Lewy bodies (DLB) remains unknown. Our analyses reveal that lipid rafts from DLB exhibit aberrant lipid profiles including low levels of n-3 long-chain polyunsaturated fatty acids (mainly docosahexaenoic acid), plasmalogens and cholesterol, and reduced unsaturation and peroxidability indexes...
September 6, 2016: Neurobiology of Aging
Binod Kumar, Dipanjan Dutta, Jawed Iqbal, Mairaj Ahmed Ansari, Arunava Roy, Leela Chikoti, Gina Pisano, Mohanan Valiya Veettil, Bala Chandran
Kaposi's sarcoma-associated herpesvirus (KSHV) binding to the endothelial cell surface heparan sulfate is followed by sequential interactions with α3β1, αVβ3 and αVβ5 integrins and Ephrin A2 receptor tyrosine kinase (EphA2R). These interactions activate host cell pre-existing FAK, Src, PI3-K and RhoGTPase signaling cascades, c-Cbl mediated ubiquitination of receptors, recruitment of CIB1, p130Cas and Crk adaptor molecules, and membrane bleb formation leading to lipid raft dependent macropinocytosis of KSHV into human microvascular dermal endothelial (HMVEC-d) cells...
October 2016: PLoS Pathogens
Margarida Ressurreição, Firat Elbeyioglu, Ruth S Kirk, David Rollinson, Aidan M Emery, Nigel M Page, Anthony J Walker
During infection of their human definitive host, schistosomes transform rapidly from free-swimming infective cercariae in freshwater to endoparasitic schistosomules. The 'somules' next migrate within the skin to access the vasculature and are surrounded by host molecules that might activate intracellular pathways that influence somule survival, development and/or behaviour. However, such 'transactivation' by host factors in schistosomes is not well defined. In the present study, we have characterized and functionally localized the dynamics of protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) activation during early somule development in vitro and demonstrate activation of these protein kinases by human epidermal growth factor, insulin, and insulin-like growth factor I, particularly at the parasite surface...
October 20, 2016: Scientific Reports
Weiwei Luo, Zi Zhao Lieu, Ed Manser, Alexander D Bershadsky, Michael P Sheetz
A nodal cytoplasmic actin network underlies actin cytoplasm cohesion in the absence of stress fibers. We previously described such a network that forms upon Latrunculin A (LatA) treatment, in which formin DAAM1 was localized at these nodes. Knock down of DAAM1 reduced the mobility of actin nodes but the nodes remained. Here we have investigated DAAM1 containing nodes after LatA washout. DAAM1 was found to be distributed between the cytoplasm and the plasma membrane. The membrane binding likely occurs through an interaction with lipid rafts, but is not required for F-actin assembly...
2016: PloS One
Tzu-Pin Shentu, Ming He, Xiaoli Sun, Jianlin Zhang, Fan Zhang, Brendan Gongol, Traci L Marin, Jiao Zhang, Liang Wen, Yinsheng Wang, Gregory G Geary, Yi Zhu, David A Johnson, John Y-J Shyy
OBJECTIVE: Cortactin translocates to the cell periphery in vascular endothelial cells (ECs) on cortical-actin assembly in response to pulsatile shear stress. Because cortactin has putative sites for AMP-activated protein kinase (AMPK) phosphorylation and sirtuin 1 (SIRT1) deacetylation, we examined the hypothesis that AMPK and SIRT1 coregulate cortactin dynamics in response to shear stress. APPROACH AND RESULTS: Analysis of the ability of AMPK to phosphorylate recombinant cortactin and oligopeptides whose sequences matched AMPK consensus sequences in cortactin pointed to Thr-401 as the site of AMPK phosphorylation...
October 6, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Mariana Certal, Adriana Vinhas, Aurora Barros-Barbosa, Fátima Ferreirinha, Maria Adelina Costa, Paulo Correia-de-Sá
Nucleotides released during heart injury affect myocardium electrophysiology and remodelling through P2 purinoceptors activation in cardiac myofibroblasts. ATP and UTP endorse [Ca(2) +]i accumulation and growth of DDR-2/a-SMA-expressing myofibroblasts from adult rat ventricles via P2Y4 and P2Y2 receptors activation, respectively. Ventricular myofibroblasts also express ADP-sensitive P2Yi, P2Yi2 and P2Yi3 receptors as demonstrated by immunofluorescence confocal microscopy and western blot analysis, but little information exists on ADP effects in these cells...
October 18, 2016: Journal of Cellular Physiology
Evangelia Gavgiotaki, George Filippidis, Haris Markomanolaki, George Kenanakis, Sofia Agelaki, Vassilis Georgoulias, Irene Athanassakis
Third Harmonic Generation (THG) microscopy as a non-invasive, label free imaging methodology, allows linkage of lipid profiles with various breast cancer cells. The collected THG signal arise mostly from the lipid droplets and the membrane lipid bilayer. Quantification of THG signal can accurately distinguish HER2-positive cells. Further analysis using Fourier transform infrared (FTIR) spectra reveals cancer-specific profiles, correlating lipid raft-corresponding spectra to THG signal, associating thus THG to chemical information...
October 18, 2016: Journal of Biophotonics
Jorge Bernardino de la Serna, Gerhard J Schütz, Christian Eggeling, Marek Cebecauer
Ever since technologies enabled the characterization of eukaryotic plasma membranes, heterogeneities in the distributions of its constituents were observed. Over the years this led to the proposal of various models describing the plasma membrane organization such as lipid shells, picket-and-fences, lipid rafts, or protein islands, as addressed in numerous publications and reviews. Instead of emphasizing on one model we in this review give a brief overview over current models and highlight how current experimental work in one or the other way do not support the existence of a single overarching model...
2016: Frontiers in Cell and Developmental Biology
Haruka Imai, Tsuyoshi Fujita, Mikihito Kajiya, Kazuhisa Ouhara, Tetsuya Yoshimoto, Shinji Matsuda, Katsuhiro Takeda, Hidemi Kurihara
BACKGROUND: An investigation of the mechanisms underlying the production of inflammatory cytokines through the stimulation of microorganisms on gingival epithelial cells may provide insights into the pathogenesis of the initiation of periodontitis. Lipid rafts, microdomains in the cell membrane, include a large number of receptors, and are centrally involved in signal transduction. We herein examined the involvement of lipid rafts in the expression of interleukin (IL-6) and IL-8 in gingival epithelial cells stimulated by periodontal pathogens...
October 17, 2016: Cellular Physiology and Biochemistry
Akira Takashima, Daiju Fukuda, Kimie Tanaka, Yasutomi Higashikuni, Yoichiro Hirata, Sachiko Nishimoto, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Yutaka Taketani, Michio Shimabukuro, Masataka Sata
BACKGROUND AND AIMS: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are major components of n-3 polyunsaturated fatty acids (n-3 PUFAs) which inhibit atherogenesis, although few studies have examined the effects of the combination of EPA and DHA on atherogenesis. The aim of this study was to investigate whether DHA has additional anti-atherosclerotic effects when combined with EPA. METHODS: Male 8-week-old apolipoprotein E-deficient (Apoe(-/-)) mice were fed a western-type diet supplemented with different amounts of EPA and DHA; EPA (2...
October 5, 2016: Atherosclerosis
Benjamin E Brummel, Anthony R Braun, Jonathan N Sachs
Using molecular dynamics simulations, we have explored the effect of asymmetric lipids-specifically those that contain one polyunsaturated (PUFA) and one saturated fatty acid chain-on phase separation in heterogeneous membranes. These lipids are prevalent in neuronal membranes, particularly in synaptic membranes, where the Parkinson's Disease protein α-Synuclein (αS) is found. We have therefore explored the relationship between asymmetric, PUFA-containing lipids, and αS. The simulations show that asymmetric lipids partition to the liquid disordered (Ld) phase of canonical raft mixtures because of the highly disordered PUFA chain...
October 12, 2016: Biochimica et Biophysica Acta
Hitoshi Nakayama, Hidetake Kurihara, Yasu S Morita, Taroh Kinoshita, Laura Mauri, Alessandro Prinetti, Sandro Sonnino, Noriko Yokoyama, Hideoki Ogawa, Kenji Takamori, Kazuhisa Iwabuchi
Pathogenic mycobacteria use virulence factors, including mannose-capped lipoarabinomannan (ManLAM), to survive in host phagocytic cells, such as neutrophils. We assessed the roles of lactosylceramide (LacCer, CDw17)-enriched lipid rafts in the phagocytosis of mycobacteria by human neutrophils and in the intracellular fate of phagocytosed mycobacteria. We showed that the association of the Src family kinase (SFK) Lyn with C24 fatty acid chain-containing LacCer was essential for the phagocytosis of mycobacteria by neutrophils...
October 11, 2016: Science Signaling
Duncan Hieu M Dam, Xiao-Qi Wang, Sarah Sheu, Mahima Vijay, Desmond Shipp, Luke Miller, Amy S Paller
Activation of insulin-like growth factor-1 (IGF-1) receptor (IGF1R) signaling induces keratinocyte migration, but little is known about its regulation, including in diabetic wounds. GM3, a lipid raft ganglioside synthesized by GM3 synthase (GM3S), regulates receptor signaling. In diabetic mice, knockout or topically-applied nanoconstruct-mediated knockdown of GM3S promotes wound edge IGF1R phosphorylation and re-epithelialization. Through modulating GM3 expression, we explored the role of GM3 in regulating human keratinocyte IGF1R signaling...
October 8, 2016: Journal of Investigative Dermatology
Sumita Chakrabarti, Andrew Chang, Nai-Jiang Liu, Alan R Gintzler
Caveolin-1 is the predominant structural protein of caveolae, a subset of (lipid) membrane rafts that compartmentalize cell signaling. Caveolin-1 binds most to G protein-coupled receptors and their signaling partners, thereby enhancing interactions among signaling cascade components and the relative activation of specific G protein-coupled pathways. This study reveals that chronic opioid exposure of μ-opioid receptor (MOR) expressing Chinese hamster ovary cells (MOR-CHO) and chronic in vivo morphine exposure of rat spinal cord augmented recruitment of multiple components of MOR-adenylyl cyclase (AC) stimulatory signaling by caveolin-1...
October 10, 2016: Journal of Neurochemistry
Maria Goiko, John R de Bruyn, Bryan Heit
The plasma membrane is a heterogeneous environment characterized by anomalous diffusion and the presence of microdomains that are molecularly distinct from the bulk membrane. Using single particle tracking of the C-type lectin CD93, we have identified for the first time the transient trapping of transmembrane proteins in cage-like microdomains which restrict protein diffusion. These cages are stabilized by actin-dependent confinement regions, but are separate structures with sizes and lifespans uncorrelated to those of the underlying actin corral...
October 11, 2016: Scientific Reports
Masaya Takehara, Teruhisa Takagishi, Soshi Seike, Kyohei Oishi, Yoshino Fujihara, Kazuaki Miyamoto, Keiko Kobayashi, Masahiro Nagahama
Clostridium perfringens type A, a Gram-positive, anaerobic bacterium, causes gas gangrene. Recently, we reported that C. perfringens α-toxin blocked neutrophil differentiation in an enzyme activity-dependent manner to impair host innate immunity, which should be crucial for the pathogenesis of C. perfringens. However, the detailed mechanism remains unclear. Lipid rafts have been reported to be platforms for signaling molecules involved in the regulation of cell differentiation in many different cell types...
2016: Biological & Pharmaceutical Bulletin
Tomáš Kroupa, Hana Langerová, Michal Doležal, Jan Prchal, Vojtěch Spiwok, Eric Hunter, Michaela Rumlová, Richard Hrabal, Tomáš Ruml
Matrix proteins play a key role in the transport of retroviral proteins inside infected cells and in the interaction with cellular membranes. In most retroviruses, retroviral matrix proteins are N-terminally myristoylated. This modification serves as a membrane targeting signal and also as an anchor for the membrane interaction. The aim of this work was to characterize interactions anchoring retroviral matrix protein at the plasma membrane of infected cell. To address this issue, we compared the structures and membrane affinity of the Mason-Pfizer monkey virus (M-PMV) wild-type matrix protein with its two budding deficient double mutants, i...
October 7, 2016: Journal of Molecular Biology
Mateusz Adamiak, Malwina Suszynska, Ahmed Abdel-Latif, Ahmed Abdelbaset-Ismail, Janina Ratajczak, Mariusz Z Ratajczak
Migration and bone marrow (BM) homing of hematopoietic stem progenitor cells (HSPCs) is regulated by several signaling pathways, and here we provide evidence for the involvement in this process of hematopoietic-specific phospholipase C-β2 (PLC-β2). This enzyme is involved in release of intracellular calcium and activation of protein kinase C (PKC). Recently we reported that PLC-β2 promotes mobilization of HSPCs from BM into peripheral blood (PB), and this effect is mediated by the involvement of PLC-β2 in the release of proteolytic enzymes from granulocytes and its role in disintegration of membrane lipid rafts...
October 4, 2016: Stem Cell Reviews
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