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https://www.readbyqxmd.com/read/27930836/hepatitis-c-virus-infection-propagates-through-interactions-between-syndecan-1-and-cd81-and-impacts-the-hepatocyte-glycocalyx
#1
Boyan Grigorov, Emma Reungoat, Alice Gentil Dit Maurin, Mihayl Varbanov, Julie Blaising, Maud Michelet, Rachel Manuel, Romain Parent, Birke Bartosch, Fabien Zoulim, Florence Ruggiero, Eve-Isabelle Pécheur
The hepatitis C virus (HCV) infects hepatocytes after binding to heparan sulfate proteoglycans (HSPG), in particular Syndecan-1, followed by recognition of the tetraspanin CD81 and other receptors. HSPGs are found in a specific microenvironment coating the hepatocyte surface called the glycocalyx, and are receptors for extracellular matrix proteins, cytokines, growth factors, lipoproteins and infectious agents. We investigated the mutual influence of HCV infection on the glycocalyx, and revealed new links between Syndecan-1 and CD81...
December 8, 2016: Cellular Microbiology
https://www.readbyqxmd.com/read/27916518/mechanism-of-structural-tuning-of-the-hepatitis-c-virus-human-cellular-receptor-cd81-large-extracellular-loop
#2
Eva S Cunha, Pedro Sfriso, Adriana L Rojas, Adam Hospital, Modesto Orozco, Nicola G A Abrescia
Hepatitis C virus (HCV) enters into human hepatocytes via tetraspanin hCD81. HCV glycoprotein E2 recognizes the "head" subdomain of the large extracellular loop (LEL) of CD81 (hCD81LEL), but the precise mechanism of virus cell attachment and entry remains elusive. Here, by combining the structural analysis of a conspicuous number of crystallized CD81LEL molecules with molecular dynamics simulations, we show that the conformational plasticity of the hCD81LEL head subdomain is a molecular property of the receptor...
November 21, 2016: Structure
https://www.readbyqxmd.com/read/27894104/proteomic-profiling-of-nci-60-extracellular-vesicles-uncovers-common-protein-cargo-and-cancer-type-specific-biomarkers
#3
Stephanie N Hurwitz, Mark A Rider, Joseph L Bundy, Xia Liu, Rakesh K Singh, David G Meckes
Packed with biological information, extracellular vesicles (EVs) offer exciting promise for biomarker discovery and applications in therapeutics and non-invasive diagnostics. Currently, our understanding of EV contents is confined by the limited cells from which vesicles have been characterized utilizing the same enrichment method. Using sixty cell lines from the National Cancer Institute (NCI-60), here we provide the largest proteomic profile of EVs in a single study, identifying 6,071 proteins with 213 common to all isolates...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888619/tetraspanin-cd151-as-an-emerging-potential-poor-prognostic-factor-across-solid-tumors-a-systematic-review-and-meta-analysis
#4
REVIEW
Ping Zeng, Yin-Hua Wang, Meng Si, Jin-Hua Gu, Ping Li, Pei-Hua Lu, Min-Bin Chen
Tetraspanin CD151, also known as PETA-3 or SFA-1, has been reported to predict prognosis in various solid tumors. Yet, the results of these studies remained inconclusive. Here, we performed this meta-analysis of relevant studies published on the topic to quantitatively evaluate the clinicopathological significance of CD151 in solid tumors. The relevant articles were identified via searching the PubMed, Web of Science and Embase database. The pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CI) of overall survival (OS) and disease-free survival (DFS) were calculated to evaluate the prognostic value of CD151 expression in patients with solid tumors...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27882487/delivery-of-small-interfering-rna-to-inhibit-vascular-endothelial-growth-factor-in-zebrafish-using-natural-brain-endothelia-cell-secreted-exosome-nanovesicles-for-the-treatment-of-brain-cancer
#5
Tianzhi Yang, Brittany Fogarty, Bret LaForge, Salma Aziz, Thuy Pham, Leanne Lai, Shuhua Bai
Although small interfering RNA (siRNA) holds great therapeutic promise, its delivery to the disease site remains a paramount obstacle. In this study, we tested whether brain endothelial cell-derived exosomes could deliver siRNA across the blood-brain barrier (BBB) in zebrafish. Natural exosomes were isolated from brain endothelial bEND.3 cell culture media and vascular endothelial growth factor (VEGF) siRNA was loaded in exosomes with the assistance of a transfection reagent. While fluorescence-activated cell flow cytometry and immunocytochemistry staining studies indicated that wild-type exosomes significantly increased the uptake of fluorescence-labeled siRNA in the autologous brain endothelial cells, decreased fluorescence intensity was observed in the cells treated with the tetraspanin CD63 antibody-blocked exosome-delivered formulation (p < 0...
November 23, 2016: AAPS Journal
https://www.readbyqxmd.com/read/27881302/crystal-structure-of-a-full-length-human-tetraspanin-reveals-a-cholesterol-binding-pocket
#6
Brandon Zimmerman, Brendan Kelly, Brian J McMillan, Tom C M Seegar, Ron O Dror, Andrew C Kruse, Stephen C Blacklow
Tetraspanins comprise a diverse family of four-pass transmembrane proteins that play critical roles in the immune, reproductive, genitourinary, and auditory systems. Despite their pervasive roles in human physiology, little is known about the structure of tetraspanins or the molecular mechanisms underlying their various functions. Here, we report the crystal structure of human CD81, a full-length tetraspanin. The transmembrane segments of CD81 pack as two largely separated pairs of helices, capped by the large extracellular loop (EC2) at the outer membrane leaflet...
November 3, 2016: Cell
https://www.readbyqxmd.com/read/27879451/tetraspanins-and-mouse-oocyte-microvilli-related-to-fertilizing-ability
#7
Achraf Benammar, Ahmed Ziyyat, Brigitte Lefèvre, Jean-Philippe Wolf
Our electron microscopy observations demonstrate for the first time that the number of microvilli on the mice oocyte membrane decreases when meiosis progresses from prophase I to metaphase II (MII) stage, and the morphology of the microvilli also changes. Microvilli are significantly shorter and larger on the ovulated oocyte membrane than at the previous stages. Although clathrin vesicles clearly disappear during oocyte maturation, exosome-like vesicles begin to be secreted at the metaphase I stage, more strongly at the MII stage...
November 21, 2016: Reproductive Sciences
https://www.readbyqxmd.com/read/27868074/cd63-promotes-hemocyte-mediated-phagocytosis-in-the-clam-paphia-undulata
#8
Mingjia Yu, Shanjun Yang, Hongxia Sun, Qiang Xia
As one of the surface membrane proteins of tetraspanin family, CD63 plays a crucial role in cellular trafficking and endocytosis, which also is associated with activation of a wide variety of immune cells. Here, the homolog of CD63 was characterized from one marine mollusk, Paphia undulata, which is designated as Pu-CD63. The complete cDNA of Pu-CD63 is 1,738 bp in length with an open reading frame (ORF) of 849 bp, encoding a 282 amino acid protein with four putative hydrophobic transmembrane helixes. Bioinformatic analysis revealed that Pu-CD63 contains one putative YXXØ consensus motif of "110-YVII-113" and one N-glycosylation site "155-NGT-157" within the large extracellular loop (LEL) region, supporting its conserved function in plasma membrane and endosomal/lysosomal trafficking...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27853258/digital-detection-of-exosomes-by-interferometric-imaging
#9
George G Daaboul, Paola Gagni, Luisa Benussi, Paolo Bettotti, Miriam Ciani, Marina Cretich, David S Freedman, Roberta Ghidoni, Ayca Yalcin Ozkumur, Chiara Piotto, Davide Prosperi, Benedetta Santini, M Selim Ünlü, Marcella Chiari
Exosomes, which are membranous nanovesicles, are actively released by cells and have been attributed to roles in cell-cell communication, cancer metastasis, and early disease diagnostics. The small size (30-100 nm) along with low refractive index contrast of exosomes makes direct characterization and phenotypical classification very difficult. In this work we present a method based on Single Particle Interferometric Reflectance Imaging Sensor (SP-IRIS) that allows multiplexed phenotyping and digital counting of various populations of individual exosomes (>50 nm) captured on a microarray-based solid phase chip...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27833910/extracellular-microvesicle-production-by-human-eosinophils-activated-by-inflammatory-stimuli
#10
Praveen Akuthota, Lívia A S Carmo, Kennedy Bonjour, Ryann O Murphy, Thiago P Silva, Juliana P Gamalier, Kelsey L Capron, John Tigges, Vasilis Toxavidis, Virginia Camacho, Ionita Ghiran, Shigeharu Ueki, Peter F Weller, Rossana C N Melo
A key function of human eosinophils is to secrete cytokines, chemokines and cationic proteins, trafficking, and releasing these mediators for roles in inflammation and other immune responses. Eosinophil activation leads to secretion of pre-synthesized granule-stored mediators through different mechanisms, but the ability of eosinophils to secrete extracellular vesicles (EVs), very small vesicles with preserved membrane topology, is still poorly understood. In the present work, we sought to identify and characterize EVs released from human eosinophils during different conditions: after a culturing period or after isolation and stimulation with inflammatory stimuli, which are known to induce eosinophil activation and secretion: CCL11 (eotaxin-1) and tumor necrosis factor alpha (TNF-α)...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27818281/gpr56-adgrg1-activation-promotes-melanoma-cell-migration-via-ntf-dissociation-and-ctf-mediated-g%C3%AE-12-13-rhoa-signaling
#11
Nien-Yi Chiang, Yen-Ming Peng, Horng-Heng Juang, Tse-Ching Chen, Hsiao-Lin Pan, Gin-Wen Chang, Hsi-Hsien Lin
GPR56/ADGRG1 is a versatile adhesion G protein-coupled receptor with diverse biological functions. GPR56 expression is variably detected in human melanoma cell lines and correlates inversely with the metastatic potential of melanoma lesions. GPR56 associates with the tetraspanins CD9 and CD81 on melanoma cell surface. GPR56 activation by immobilized CG4 mAb facilitates NTF dissociation in a CD9/CD81-dependent manner specifically inducing IL-6 production, which promotes cell migration and invasion. Interestingly, expression of GPR56-CTF alone recapitulates the antibody-induced receptor function, implicating a major role for the CTF in GPR56 activation and signaling...
November 3, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27818272/tetraspanin-3-a-central-endocytic-membrane-component-regulating-the-expression-of-adam10-presenilin-and-the-amyloid-precursor-protein
#12
Lisa Seipold, Markus Damme, Johannes Prox, Björn Rabe, Petr Kasparek, Radislav Sedlacek, Hermann Altmeppen, Michael Willem, Barry Boland, Markus Glatzel, Paul Saftig
Despite existing knowledge about the role of the A Disintegrin and Metalloproteinase 10 (ADAM10) as the α-secretase involved in the non-amyloidogenic processing of the amyloid precursor protein (APP) and Notch signalling we have only limited information about its regulation. In this study, we have identified ADAM10 interactors using a split ubiquitin yeast two hybrid approach. Tetraspanin 3 (Tspan3), which is highly expressed in the murine brain and elevated in brains of Alzheimer´s disease (AD) patients, was identified and confirmed to bind ADAM10 by co-immunoprecipitation experiments in mammalian cells in complex with APP and the γ-secretase protease presenilin...
January 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27784871/the-role-of-tetraspanin-cd9-in-osteoarthritis-using-three-different-mouse-models
#13
Norihiko Sumiyoshi, Hiroyuki Ishitobi, Shigeru Miyaki, Kenji Miyado, Nobuo Adachi, Mitsuo Ochi
Although osteoarthritis (OA) is the most prevalent aging-related joint disease, the understanding of mechanisms of OA pathogenesis remains limited. Key features include the progressive degradation of articular cartilage, synovial hyperplasia, and angiogenesis in joint tissues. CD9, a member of the tetraspanin family, is localized in the cell membranes and partly in the endosomes of all mammalian cell types. CD9 is associated with inflammation and angiogenesis through cell adhesion, migration, and signal transduction...
2016: Biomedical Research
https://www.readbyqxmd.com/read/27780340/cd9-expression-in-colorectal-carcinomas-and-its-prognostic-significance
#14
Kyung-Ju Kim, Hee Jung Kwon, Min Chong Kim, Young Kyung Bae
BACKGROUND: CD9, a member of the tetraspanin superfamily, is a tumor suppressor in many malignancies. The aim of this study was to evaluate the immunohistochemical expression of CD9 in colorectal carcinomas (CRCs) and determine clinicopathological and prognostic significance of its expression. METHODS: The CD9 expression status of 305 CRCs was evaluated using a semi-quantitative scoring system in tumor cells (T-CD9) and immune cells (I-CD9) by classifying the results as high and low expression...
November 2016: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/27763528/up-regulation-of-claudin-6-in-the-distal-lung-impacts-secondhand-smoke-induced-inflammation
#15
Joshua B Lewis, Dallin C Milner, Adam L Lewis, Todd M Dunaway, Kaleb M Egbert, Scott C Albright, Brigham J Merrell, Troy D Monson, Dallin S Broberg, Jason R Gassman, Daniel B Thomas, Juan A Arroyo, Paul R Reynolds
It has long been understood that increased epithelial permeability contributes to inflammation observed in many respiratory diseases. Recently, evidence has revealed that environmental exposure to noxious material such as cigarette smoke reduces tight junction barrier integrity, thus enhancing inflammatory conditions. Claudin-6 (Cldn6) is a tetraspanin transmembrane protein found within the tight junctional complex and is implicated in maintaining lung epithelial barriers. To test the hypothesis that increased Cldn6 ameliorates inflammation at the respiratory barrier, we utilized the Tet-On inducible transgenic system to conditionally over-express Clnd6 in the distal lung...
October 17, 2016: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/27760757/assessment-of-cd37-b-cell-antigen-and-cell-of-origin-significantly-improves-risk-prediction-in-diffuse-large-b-cell-lymphoma
#16
Zijun Y Xu-Monette, Ling Li, John C Byrd, Kausar J Jabbar, Ganiraju C Manyam, Charlotte Maria de Winde, Michiel van den Brand, Alexandar Tzankov, Carlo Visco, Jing Wang, Karen Dybkaer, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L Richards, Eric D Hsi, William W L Choi, Jooryung Huh, Maurilio Ponzoni, Andrés J M Ferreri, Michael B Møller, Ben M Parsons, Jane N Winter, Michael Wang, Fredrick B Hagemeister, Miguel A Piris, J Han van Krieken, L Jeffrey Medeiros, Yong Li, Annemiek B van Spriel, Ken H Young
CD37 (tetraspanin TSPAN26) is a B-cell surface antigen widely expressed on mature B-cells. CD37 is involved in immune regulation and tumor suppression but its function has not been fully elucidated. In this study, we assessed CD37 expression in de novo diffuse large B-cell lymphoma (DLBCL), and investigated its clinical and biologic significance in 773 patients treated with rituximab-CHOP and 231 patients treated with CHOP chemotherapy. We found CD37 loss (CD37(-)) in ~60% of DLBCL predicted significantly decreased survival rates in R-CHOP-treated patients, independent of the International Prognostic Index (IPI), germinal-center-B-cell-like (GCB)/activated-B-cell-like (ABC) cell-of-origin, nodal/extranodal primary origin, and the prognostic factors associated with CD37(-), including TP53 mutation, NF-κB(high), Myc(high), p-STAT3(high), survivin(high), p63(-), and BCL6 translocation...
October 19, 2016: Blood
https://www.readbyqxmd.com/read/27740621/tetraspanin-cd9-stabilizes-gp130-by-preventing-its-ubiquitin-dependent-lysosomal-degradation-to-promote-stat3-activation-in-glioma-stem-cells
#17
Yu Shi, Wenchao Zhou, Lin Cheng, Cong Chen, Zhi Huang, Xiaoguang Fang, Qiulian Wu, Zhicheng He, Senlin Xu, Justin D Lathia, Yifang Ping, Jeremy N Rich, Xiu-Wu Bian, Shideng Bao
Glioblastoma (GBM) is the most malignant and lethal brain tumor harboring glioma stem cells (GSCs) that promote tumor propagation and therapeutic resistance. GSCs preferentially express several critical cell surface molecules that regulate the pro-survival signaling for maintaining the stem cell-like phenotype. Tetraspanin CD9 has recently been reported as a GSC biomarker that is relevant to the GSC maintenance. However, the underlying molecular mechanisms of CD9 in maintaining GSC property remain elusive. Herein, we report that CD9 stabilizes the IL-6 receptor glycoprotein 130 (gp130) by preventing its ubiquitin-dependent lysosomal degradation to facilitate the STAT3 activation in GSCs...
October 14, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27736296/stem-cells-migration-during-skeletal-muscle-regeneration-the-role-of-sdf-1-cxcr4-and-sdf-1-cxcr7-axis
#18
Kamil Kowalski, Aleksandra Kołodziejczyk, Maria Helena Sikorska, Jagoda Płaczkiewicz, Paulina Cichosz, Magdalena Kowalewska, Wladyslawa Streminska, Katarzyna Janczyk-Ilach, Marta Koblowska, Anna Fogtman, Roksana Iwanicka-Nowicka, Maria A Ciemerych, Edyta Brzoska
The skeletal muscle regeneration occurs due to the presence of tissue specific stem cells - satellite cells. These cells, localized between sarcolemma and basal lamina, are bound to muscle fibers and remain quiescent until their activation upon muscle injury. Due to pathological conditions, such as extensive injury or dystrophy, skeletal muscle regeneration is diminished. Among the therapies aiming to ameliorate skeletal muscle diseases are transplantations of the stem cells. In our previous studies we showed that Sdf-1 (stromal derived factor -1) increased migration of stem cells and their fusion with myoblasts in vitro...
October 13, 2016: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/27679865/characterization-of-tetraspanin-protein-cd81-in-mouse-spermatozoa-and-bovine-gametes
#19
Jana Jankovicova, Michaela Frolikova, Natasa Sebkova, Michal Simon, Petra Cupperova, Denisa Lipcseyova, Katarina Michalkova, Lubica Horovska, Radislav Sedlacek, Pavel Stopka, Jana Antalikova, Katerina Dvorakova-Hortova
Sperm-egg interaction and fusion represents a key moment of fertilization and it would not happen in mammals without the interaction of the tetraspanin superfamily members including protein CD81. A detailed immunohistochemical localization of CD81 was monitored on bovine oocytes of different maturation stages, as well as during early embryogenesis. There was also a CD81characterization on bovine and mouse sperm carried out. On bovine eggs, CD81 was detected on the plasma membrane of the germinal vesicle, metaphase I and metaphase II oocytes...
September 27, 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/27648936/kitenin-functions-as-a-fine-regulator-of-erbb4-expression-level-in-colorectal-cancer-via-protection-of-erbb4-from-e3-ligase-nrdp1-mediated-degradation
#20
Eun Gene Sun, Kyung Hwa Lee, Yoo-Seung Ko, Hui Jeong Choi, Jung-In Yang, Jae Hyuk Lee, Ik Joo Chung, Yun-Woong Paek, Hangun Kim, Jeong A Bae, Kyung Keun Kim
Understanding the complex biological functions of E3-ubiquitin ligases may facilitate the development of mechanism-based anti-cancer drugs. We recently identified that the KITENIN/ErbB4-Dvl2-c-Jun axis works as a novel unconventional downstream signal of epidermal growth factor (EGF) in colorectal cancer (CRC) tissues. Here we addressed whether E3-ubiquitin ligases are required for operation of this axis. We found that Nrdp1, an E3-ligase for ErbB3/ErbB4, interacted with KITENIN (KAI1 C-terminal interacting tetraspanin) to form a functional KITENIN/ErbB4/Nrdp1 complex and is responsible for down-regulating Dvl2 within this complex...
September 20, 2016: Molecular Carcinogenesis
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