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https://www.readbyqxmd.com/read/29020490/impact-of-ticagrelor-on-p2y1-and-p2y12-localization-and-on-cholesterol-levels-in-platelet-plasma-membrane
#1
Vahideh Rabani, Damien Montange, Nicolas Meneveau, Siamak Davani
Ticagrelor is an antiplatelet agent that inhibits platelet activation via P2Y12 antagonism. There are several studies showing that P2Y12 needs lipid rafts to be activated, but there are few data about how ticagrelor impacts lipid raft organization. Therefore, we aimed to investigate how ticagrelor could impact the distribution of cholesterol and consequently alter the organization of lipid rafts on platelet plasma membranes. We identified cholesterol-enriched raft fractions in platelet membranes by quantification of their cholesterol levels...
October 11, 2017: Platelets
https://www.readbyqxmd.com/read/28930577/exosome-enrichment-by-ultracentrifugation-and-size-exclusion-chromatography
#2
Yong Qin Koh, Fatema B Almughlliq, Kanchan Vaswani, Hassendrini N Peiris, Murray D Mitchell
Exosomes are a subset of extracellular vesicles (EVs) that have important roles in intercellular communication. They contain and carry bioactive molecules within their membranes which are delivered to target cells. Reproducible isolation and enrichment of these exosomes will aid in evaluation of cellular communication. We present an approach that involved the pre-processing of plasma, combined with ultracentrifugation (UC) and size exclusion chromatography (SEC) to isolate EVs and subsequently enrich exosomes...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28919558/cellular-uptake-of-extracellular-vesicles-is-mediated-by-clathrin-independent-endocytosis-and-macropinocytosis
#3
Helena Costa Verdera, Jerney J Gitz-Francois, Raymond M Schiffelers, Pieter Vader
Recent evidence has established that extracellular vesicles (EVs), including exosomes and microvesicles, form an endogenous transport system through which biomolecules, including proteins and RNA, are exchanged between cells. This endows EVs with immense potential for drug delivery and regenerative medicine applications. Understanding the biology underlying EV-based intercellular transfer of cargo is of great importance for the development of EV-based therapeutics. Here, we sought to characterize the cellular mechanisms involved in EV uptake...
September 14, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28881760/prognostic-value-of-flotillin-1-expression-in-patients-with-solid-tumors
#4
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...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28865798/mpp1-directly-interacts-with-flotillins-in-erythrocyte-membrane-possible-mechanism-of-raft-domain-formation
#5
Agnieszka Biernatowska, Katarzyna Augoff, Joanna Podkalicka, Sabina Tabaczar, Weronika Gajdzik-Nowak, Aleksander Czogalla, Aleksander F Sikorski
Flotillins are prominent, oligomeric protein components of erythrocyte (RBC) membrane raft domains and are considered to play an important structural role in lateral organization of the plasma membrane. In our previous work on erythroid membranes and giant plasma membrane vesicles (GPMVs) derived from them we have shown that formation of functional domains (resting state rafts) depends on the presence of membrane palmitoylated protein 1 (MPP1/p55), pointing to its new physiological role. Exploration of the molecular mechanism of MPP1 function in organizing membrane domains described here, through searching for its molecular partners in RBC membrane by using different methods, led to the identification of the raft-marker proteins, flotillin 1 and flotillin 2, as hitherto unreported direct MPP1 binding-partners in the RBC membrane...
September 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28825855/flotilin-1-promotes-the-tumorigenicity-and-progression-of-malignant-phenotype-in-human-lung-adenocarcinoma
#6
Ai Yun Guo, Xu Jun Liang, Rui Jie Liu, Xiao Xiao Li, Wu Bi, Liu Ying Zhou, Can E Tang, Ang Yan, Zhu Chu Chen, Peng Fei Zhang
Lung adenocarcinoma (LUAD) accounts for the most common histological subtype of lung cancer which remains the leading cause of cancer death worldwide. The discovery of more sensitive and specific novel target biomarkers for predicting the development and progression of LUAD is imperative. Flotillin-1 (Flot-1) has been reported to have important roles in the progression of several tumor types but not been reported in the progression of LUAD. Here, we demonstrated that the expression of flotillin-1 was upregulated in 5 LUAD cells...
August 21, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28821575/ldl-switches-the-lrp6-internalization-route-from-flotillin-dependent-to-clathrin-dependent-in-hepatic-cells
#7
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
#8
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
#9
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...
September 15, 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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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