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https://www.readbyqxmd.com/read/28821575/ldl-switches-the-lrp6-internalization-route-from-flotillin-dependent-to-clathrin-dependent-in-hepatic-cells
#1
Hideki Yamamoto, Daisuke Umeda, Shinji Matsumoto, Akira Kikuchi
Low-density lipoprotein (LDL) receptor-related protein 6 (LRP6) was originally identified as a coreceptor of the Wnt signaling pathway and has been shown to be involved in LDL transport. In polarized hepatocytes, many apical proteins are sorted to the basolateral membrane and then internalized and transported to the apical bile canalicular membrane-a process known as transcytosis. Herein, we show that LRP6 is transcytosed to the apical membrane of polarized hepatic HepG2 cells via a flotillin-dependent manner in the absence of LDL...
August 18, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28800633/feeding-fasting-dependent-recruitment-of-membrane-microdomain-proteins-to-lipid-droplets-purified-from-the-liver
#2
Kritika Sadh, Priyanka Rai, Roop Mallik
Lipid droplets (LDs) are cellular stores of neutral fat that facilitate lipid and protein trafficking in response to metabolic cues. Unlike other vesicles, the phospholipid membrane on the LD is a monolayer. Interestingly, this monolayer membrane has free cholesterol, and may therefore contain lipid microdomains that serve as a platform for assembling proteins involved in signal transduction, cell polarity, pathogen entry etc. In support of this, cell culture studies have detected microdomain-associated "raftophilic" proteins on LDs...
2017: PloS One
https://www.readbyqxmd.com/read/28751307/esglut4-and-chhbp-are-involved-in-the-regulation-of-glucose-homeostasis-in-the-crustacean-eriocheir-sinensis
#3
Ran Li, Jin-Ze Tian, Mo-Ran Wang, Li-Na Zhu, Jin-Sheng Sun
Glucose is an essential energy source for both vertebrates and invertebrates. In mammals, glucose uptake is mediated primarily by glucose transporters (GLUTs), members of the major facilitator superfamily (MFS) of passive transporters. Among the GLUTs, GLUT4 is the main glucose transporter in muscles and adipocytes. In skeletal muscle cells, GLUT4 interacts with the lipid raft protein flotillin to transport glucose upon stimulation by insulin. Although several studies have examined GLUT4 function in mammals, few have been performed in crustaceans, which also use glucose as their main energy source...
July 27, 2017: Biology Open
https://www.readbyqxmd.com/read/28739689/lxr-activation-down-regulates-lipid-raft-markers-flot2-and-dhhc5-in-mcf-7-breast-cancer-cells
#4
Delphine Carbonnelle, Trang H Luu, Chloe Chaillou, Jean-Michel Huvelin, Jean-Marie Bard, Hassan Nazih
BACKGROUND/AIM: Lipid rafts are cholesterol-enriched microdomains of the plasma membrane. Recent studies have underlined that their integrity is critical for cancer cell survival. Liver X receptor (LXR) has a central role in cellular cholesterol homeostasis and its stimulation inhibits proliferation of several cancer cell lines. This study investigated whether LXR could modulate lipid rafts integrity and consequently alter proliferation of the MCF-7 breast cancer cell line. MATERIALS AND METHODS: Effect of LXR agonist T0901317 on integrity of MCF-7 lipid rafts was examined by studying the expression of rafts marker flotillin-2 (FLOT2) and DHHC5, which palmitoylates FLOT2, and by studying the expression of phospho-Akt...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28732197/wrecking-staph-s-rafts-staphylococcus-aureus-no-longer-unsinkable
#5
Rafi Rashid, Kimberly A Kline
Functional membrane microdomains (FMMs) serve to spatially restrict and coordinate a diversity of cellular functions. Flotillins serve as scaffolds within FMMs, and in this issue of Cell Chemical Biology, Koch et al. (2017) show that disrupting Staphylococcus aureus scaffolds via small molecules perturbs virulence gene expression and attenuates S. aureus virulence.
July 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28697798/a-proteomic-analysis-of-lrrk2-binding-partners-reveals-interactions-with-multiple-signaling-components-of-the-wnt-pcp-pathway
#6
Alena Salašová, Chika Yokota, David Potěšil, Zbyněk Zdráhal, Vítězslav Bryja, Ernest Arenas
BACKGROUND: Autosomal-dominant mutations in the Park8 gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been identified to cause up to 40% of the genetic forms of Parkinson's disease. However, the function and molecular pathways regulated by LRRK2 are largely unknown. It has been shown that LRRK2 serves as a scaffold during activation of WNT/β-catenin signaling via its interaction with the β-catenin destruction complex, DVL1-3 and LRP6. In this study, we examine whether LRRK2 also interacts with signaling components of the WNT/Planar Cell Polarity (WNT/PCP) pathway, which controls the maturation of substantia nigra dopaminergic neurons, the main cell type lost in Parkinson's disease patients...
July 11, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28687359/identification-and-characterization-of-the-lamprey-flotillin-1-gene-with-a-role-in-cell-adhesion
#7
Rong Xu, Xiaoping Song, Peng Su, Yue Pang, Qingwei Li
Flotillin-1 is a kind of localize into specific cholesterol rich microdomains in cellular membranes and highly conserved lipid rafts marker protein widely distributed in animals and plants. It provides a platform for the reaction of many proteins in signal transduction, as scaffolding plays an important role in transmembrane signaling and cell adhesion. Here, Flotillin-1 protein from lamprey was identified and characterized (designated as L-Flotillin-1). After a partial cDNA sequence of L-Flotillin-1 was identified in a lamprey supraneural body cDNA library, the full-length cDNA was obtained using 3'- and 5'-rapid amplification of cDNA ends (RACE)...
July 4, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28669526/attenuating-staphylococcus-aureus-virulence-by-targeting-flotillin-protein-scaffold-activity
#8
Gudrun Koch, Charlotte Wermser, Ivan C Acosta, Lara Kricks, Stephanie T Stengel, Ana Yepes, Daniel Lopez
Scaffold proteins are ubiquitous chaperones that bind proteins and facilitate physical interaction of multi-enzyme complexes. Here we used a biochemical approach to dissect the scaffold activity of the flotillin-homolog protein FloA of the multi-drug-resistant human pathogen Staphylococcus aureus. We show that FloA promotes oligomerization of membrane protein complexes, such as the membrane-associated RNase Rny, which forms part of the RNA-degradation machinery called the degradosome. Cells lacking FloA had reduced Rny function and a consequent increase in the targeted sRNA transcripts that negatively regulate S...
July 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28668965/membrane-remodelling-and-vesicle-formation-during-ageing-of-human-red-blood-cells
#9
Annarita Ciana, Cesare Achilli, Anjali Gaur, Giampaolo Minetti
BACKGROUND/AIMS: A high surface-to-volume ratio and a spectrin membrane-skeleton (MS) confer to the mammalian red blood cells (RBCs) their characteristic deformability, mechanical strength and structural stability. During their 120 days of circulatory life in humans, RBCs decrease in size, while remaining biconcave disks, owing to a coordinated decrease in membrane surface area and cell water. It is generally believed that part of the membrane is lost with the shedding of spectrin-free vesicles of the same type that can be obtained in vitro by different treatments...
June 30, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28666573/mlkl-the-protein-that-mediates-necroptosis-also-regulates-endosomal-trafficking-and-extracellular-vesicle-generation
#10
Seongmin Yoon, Andrew Kovalenko, Konstantin Bogdanov, David Wallach
Activation of the pseudokinase mixed lineage kinase domain-like (MLKL) upon its phosphorylation by the protein kinase RIPK3 triggers necroptosis, a form of programmed cell death in which rupture of cellular membranes yields release of intracellular components. We report that MLKL also associated with endosomes and controlled the transport of endocytosed proteins, thereby enhancing degradation of receptors and ligands, modulating their induced signaling and facilitating the generation of extracellular vesicles...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28655199/proteins-involved-in-endocytosis-are-upregulated-by-ageing-in-the-normal-human-brain-implications-for-the-development-of-alzheimer-s-disease
#11
Mouhamed Alsaqati, Rhian S Thomas, Emma J Kidd
The greatest risk factor for Alzheimer's disease (AD) is advanced age, but the reason for this association remains unclear. Amyloid-beta (Aβ) is produced from amyloid precursor protein (APP) primarily after APP is internalised by clathrin-mediated or clathrin-independent endocytosis. Changes in endocytosis in AD have been identified. We hypothesised that endocytic protein expression is altered during ageing, thus influencing the likelihood of developing AD by increasing Aβ production. We explored how levels of endocytic proteins, APP, its metabolites, secretase enzymes and tau varied with age in cortical brain samples from men of three age ranges (young (20-30), middle-aged (45-55) and old (70-90)) with no symptoms of dementia...
June 26, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28645295/identification-of-the-flotillin-1-2-heterocomplex-as-a-target-of-autoantibodies-in-bona-fide-multiple-sclerosis
#12
S Hahn, G Trendelenburg, M Scharf, Y Denno, S Brakopp, B Teegen, C Probst, K P Wandinger, M Buttmann, A Haarmann, F Szabados, M Vom Dahl, T Kümpfel, P Eichhorn, H Gold, F Paul, S Jarius, N Melzer, W Stöcker, L Komorowski
BACKGROUND: Autoantibodies, in particular those against aquaporin-4 and myelin-oligodendrocyte glycoprotein (MOG), aid as biomarkers in the differential diagnosis of demyelination. Here, we report on discovery of autoantibodies against flotillin in patients with multiple sclerosis (MS). METHODS: The target antigen was identified by histo-immunoprecipitation using the patients' sera and cryosections of rat or pig cerebellum combined with mass spectrometrical analysis...
June 23, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28634572/a-helicobacter-pylori-homolog-of-eukaryotic-flotillin-is-involved-in-cholesterol-accumulation-epithelial-cell-responses-and-host-colonization
#13
Melanie L Hutton, Kimberley D'Costa, Amanda E Rossiter, Lin Wang, Lorinda Turner, David L Steer, Seth L Masters, Ben A Croker, Maria Kaparakis-Liaskos, Richard L Ferrero
The human pathogen Helicobacter pylori acquires cholesterol from membrane raft domains in eukaryotic cells, commonly known as "lipid rafts." Incorporation of this cholesterol into the H. pylori cell membrane allows the bacterium to avoid clearance by the host immune system and to resist the effects of antibiotics and antimicrobial peptides. The presence of cholesterol in H. pylori bacteria suggested that this pathogen may have cholesterol-enriched domains within its membrane. Consistent with this suggestion, we identified a hypothetical H...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28581508/regulation-of-cargo-transfer-between-escrt-0-and-escrt-i-complexes-by-flotillin-1-during-endosomal-sorting-of-ubiquitinated-cargo
#14
M Meister, S Bänfer, U Gärtner, J Koskimies, M Amaddii, R Jacob, R Tikkanen
Ubiquitin-dependent sorting of membrane proteins in endosomes directs them to lysosomal degradation. In the case of receptors such as the epidermal growth factor receptor (EGFR), lysosomal degradation is important for the regulation of downstream signalling. Ubiquitinated proteins are recognised in endosomes by the endosomal sorting complexes required for transport (ESCRT) complexes, which sequentially interact with the ubiquitinated cargo. Although the role of each ESCRT complex in sorting is well established, it is not clear how the cargo is passed on from one ESCRT to the next...
June 5, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28576383/cholesterol-metabolism-and-glaucoma-modulation-of-muller-cell-membrane-organization-by-24s-hydroxycholesterol
#15
Ségolène Gambert, Pierre-Henry Gabrielle, Elodie Masson, Elise Leger-Charnay, Arthur Ferrerro, Arthur Vannier, Clément Gendrault, Méline Lachot, Catherine Creuzot-Garcher, Alain Bron, Stéphane Gregoire, Laurent Leclere, Lucy Martine, Géraldine Lucchi, Caroline Truntzer, Delphine Pecqueur, Lionel Bretillon
Glaucoma is a progressive and irreversible blinding neuropathy that is characterized by the loss of retinal ganglion cells (RGCs). Muller Glial Cell (MGC) activation is induced in retinal gliosis. MGCs are the most numerous glial cells in the retina and one of their roles is to sustain cholesterol homeostasis. 24S-hydroxycholesterol (24S-OHC) is one of the form of cholesterol elimination from the retina and is overexpressed during glaucoma. The objective of this study was to determine whether 24S-OHC triggers MGC membrane dynamics involving lipid rafts and contributes to gliosis at early and late time points...
May 30, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28575093/structure-function-analysis-of-human-stomatin-a-mutation-study
#16
Stefanie Rungaldier, Ellen Umlauf, Mario Mairhofer, Ulrich Salzer, Christoph Thiele, Rainer Prohaska
Stomatin is an ancient, widely expressed, oligomeric, monotopic membrane protein that is associated with cholesterol-rich membranes/lipid rafts. It is part of the SPFH superfamily including stomatin-like proteins, prohibitins, flotillin/reggie proteins, bacterial HflK/C proteins and erlins. Biochemical features such as palmitoylation, oligomerization, and hydrophobic "hairpin" structure show similarity to caveolins and other integral scaffolding proteins. Recent structure analyses of the conserved PHB/SPFH domain revealed amino acid residues and subdomains that appear essential for the structure and function of stomatin...
2017: PloS One
https://www.readbyqxmd.com/read/28560058/flot2-promotes-tumor-growth-and-metastasis-through-modulating-cell-cycle-and-inducing-epithelial-mesenchymal-transition-of-hepatocellular-carcinoma
#17
Cheng-Hao Wang, Xiao-Dong Zhu, De-Ning Ma, Hui-Chuan Sun, Dong-Mei Gao, Ning Zhang, Cheng-Dong Qin, Yuan-Yuan Zhang, Bo-Gen Ye, Hao Cai, Wen-Kai Shi, Man-Qin Cao, Zhao-You Tang
Flotillin-2 (Flot2) is a highly conserved and ubiquitously expressed protein that resides on the cytoplasmic side of the cell membrane within specific cholesterol rich microdomains. Some studies have reported that overexpression of Flot2 is related to cancer progression. However, the role of Flot2 in hepatocellular carcinoma (HCC) remains unclarified. In this study, we aim to explore the correlation between Flot2 expression and HCC progression and the underlying mechanism. In the present study, overexpression of Flot2 in HCC tissues and cell lines was detected, and forced overexpression of Flot2 significantly promoted the proliferation, migration, invasion and metastasis of HCC in vitro and in vivo by modulating cell cycle and inducing EMT, which was mediated via up-regulation of Twist as a result of Raf/MEK/ERK1/2 pathway activation...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28535204/colocalization-of-receptors-for-shiga-toxins-with-lipid-rafts-in-primary-human-renal-glomerular-endothelial-cells-and-influence-of-d-pdmp-on-synthesis-and-distribution-of-glycosphingolipid-receptors
#18
Nadine Legros, Gottfried Pohlentz, Jana Runde, Stefanie Dusny, Hans-Ulrich Humpf, Helge Karch, Johannes Müthing
Damage of human renal glomerular endothelial cells (HRGECs) of the kidney represents the linchpin in the pathogenesis of the hemolytic uremic syndrome (HUS) caused by Shiga toxins (Stxs) of enterohemorrhagic Escherichia coli (EHEC). We performed a comprehensive structural analysis of the Stx receptor glycosphingolipids (GSLs) globotriaosylceramide (Gb3Cer, Galα4alβ4Glcβ1Cer) and globotetraosylceramide (Gb4Cer, GalNAcβ3Galα4Galβ4Glcβ1Cer) and their distribution in lipid raft analogue detergent-resistant membranes (DRMs) and nonDRMs prepared from primary HRGECs...
May 23, 2017: Glycobiology
https://www.readbyqxmd.com/read/28503944/mir-133-involves-in-lung-adenocarcinoma-cell-metastasis-by-targeting-flot2
#19
Guangxia Wei, Yahuan Xu, Tao Peng, Jie Yan
BACKGROUND: Dysregulated microRNAs (miRNAs) reported to involve into the oncogenesis and progression in various human cancers. However, the roles and mechanism of miR-133 in lung adenocarcinoma remain largely unclear. METHODS: In this study, qPCR assay and western blot were used to detect the expression levels of miR-133, Akt and FLOT2. Luciferase reporter assay was used to identify the target role of miR-133 on FLOT2. The cell invasion and the migration capability were performed using the transwell invasion assay and wound healing assay...
May 14, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28467967/prognostic-value-of-flotillin-1-expression-in-patients-with-solid-tumors
#20
Yang-xi Ou, Fang-teng Liu, Fang-ying Chen, Zheng-ming Zhu
BACKGROUND: In numerous studies, Flotillin-1 was reported to be involved in tumor progression, indicating prognosis in various types of cancer. However, the results were inconsistent. RESULTS: A total of 2473 patients from 13 articles were included. The results indicated that: (1) Patients detected with high expression level of Flotillin-1 protein had a significantly shorter OS (HR =1.64; 95%CI: 1.39-1.88), statistical significance was also observed in subgroup meta-analyses stratified by the cancer type, nationality, detecting method, cutoff value, analysis type, sample size and publication date...
April 13, 2017: Oncotarget
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