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https://www.readbyqxmd.com/read/28073834/dynamic-and-coordinated-single-molecular-interactions-at-tm4sf5-enriched-microdomains-guide-invasive-behaviors-in-2-and-3-dimensional-environments
#1
Hye-Jin Kim, Sojung Kwon, Seo Hee Nam, Jae Woo Jung, Minkyung Kang, Jihye Ryu, Ji Eon Kim, Jin-Gyu Cheong, Chang Yun Cho, Somi Kim, Dae-Geun Song, Yong-Nyun Kim, Tai Young Kim, Min-Kyo Jung, Kyung-Min Lee, Chan-Gi Pack, Jung Weon Lee
Membrane proteins sense extracellular cues and transduce intracellular signaling to coordinate directionality and speed during cellular migration. They are often localized to specific regions, as with lipid rafts or tetraspanin-enriched microdomains; however, the dynamic interactions of tetraspanins with diverse receptors within tetraspanin-enriched microdomains on cellular surfaces remain largely unexplored. Here, we investigated effects of tetraspan(in) TM4SF5 (transmembrane 4 L six family member 5)-enriched microdomains (T5ERMs) on the directionality of cell migration...
January 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28068334/two-paralogous-tetraspanins-tsp-12-and-tsp-14-function-with-the-adam10-metalloprotease-sup-17-to-promote-bmp-signaling-in-caenorhabditis-elegans
#2
Lin Wang, Zhiyu Liu, Herong Shi, Jun Liu
The highly conserved bone morphogenetic protein (BMP) signaling pathway regulates many developmental and homeostatic processes. While the core components of the BMP pathway have been well studied, much research is needed for understanding the mechanisms involved in the precise spatiotemporal control of BMP signaling in vivo. Here, we provide evidence that two paralogous and evolutionarily conserved tetraspanins, TSP-12 and TSP-14, function redundantly to promote BMP signaling in C. elegans. We further show that the ADAM10 (a disintegrin and metalloprotease 10) ortholog SUP-17 also functions to promote BMP signaling, and that TSP-12 can bind to and promote the cell surface localization of SUP-17...
January 9, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28060564/annexin-a8-promotes-vegf-a-driven-endothelial-cell-sprouting
#3
Nicole Heitzig, Benjamin F Brinkmann, Sophia N Koerdt, Gonzalo Rosso, Victor Shahin, Ursula Rescher
The physiological and pathological process of angiogenesis relies on orchestrated endothelial cell (EC) adhesion, migration and formation of new vessels. Here we report that human umbilical vein endothelial cells (HUVECs) deficient in Annexin A8 (AnxA8), a member of the annexin family of Ca(2+)- and membrane binding proteins, are strongly deficient in their ability to sprout in response to vascular endothelial growth factor (VEGF)-A, and are strongly impaired in their ability to migrate and adhere to β1 integrin-binding extracellular matrix (ECM) proteins...
January 6, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28032533/tetraspanin-tspan9-regulates-platelet-collagen-receptor-gpvi-lateral-diffusion-and-activation
#4
Elizabeth J Haining, Alexandra L Matthews, Peter J Noy, Hanna M Romanska, Helen J Harris, Jeremy Pike, Martina Morowski, Rebecca L Gavin, Jing Yang, Pierre-Emmanuel Milhiet, Fedor Berditchevski, Bernhard Nieswandt, Natalie S Poulter, Steve P Watson, Michael G Tomlinson
The tetraspanins are a superfamily of four-transmembrane proteins, which regulate the trafficking, lateral diffusion and clustering of the transmembrane proteins with which they interact. We have previously shown that tetraspanin Tspan9 is expressed on platelets. Here we have characterised gene-trap mice lacking Tspan9. The mice were viable with normal platelet numbers and size. Tspan9-deficient platelets were specifically defective in aggregation and secretion induced by the platelet collagen receptor GPVI, despite normal surface GPVI expression levels...
December 29, 2016: Platelets
https://www.readbyqxmd.com/read/28031320/tetraspanin-cd63-controls-basolateral-sorting-of-organic-cation-transporter-2-in-renal-proximal-tubules
#5
Ulf Schulze, Sabine Brast, Alexander Grabner, Christian Albiker, Beatrice Snieder, Svenja Holle, Eberhard Schlatter, Rita Schröter, Hermann Pavenstädt, Edwin Herrmann, Carsten Lambert, Gilles A Spoden, Luise Florin, Paul Saftig, Giuliano Ciarimboli
CD63 is a ubiquitously expressed member of the tetraspanin superfamily. Using a mating-based split-ubiquitin-yeast 2-hybrid system, pull-down experiments, total internal reflection fluorescence microscopy, Förster resonance energy transfer, and biotinylation assays, we found that CD63 interacts with human organic cation transporter 2 (hOCT2), which transports endogenous and exogenous substrates, such as neurotransmitters and drugs in several epithelial cells. CD63 overexpression affects cellular localization of hOCT2 expressed in human embryonic kidney (HEK)293 cells...
December 28, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28030805/timp-1-and-cd82-a-promising-combined-evaluation-marker-for-pdac
#6
Jiexin Zhang, Tijun Wu, Shanshan Zhan, Nan Qiao, Xu Zhang, Yunxia Zhu, Nan Yang, Yujie Sun, Xin A Zhang, David Bleich, Xiao Han
Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a widely secreted protein that regulates cell motility, proliferation, and apoptosis. Although it is recognized that TIMP-1-tetraspanin CD63 regulates epithelial cell apoptosis and proliferation, how TIMP-1 controls cell motility is not well understood. In this study, we identify tetraspanin CD82 (also called KAI1) as a component of the promiscuous TIMP-1 interacting protein complex on cell surface of human pancreatic adenocarcinoma cells. CD82 directly binds to TIMP-1 N-terminal region through its large extracellular loop and co-localizes with TIMP-1 in both cancer cell lines and clinical samples...
December 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/28029168/trends-in-regenerative-medicine-repigmentation-in-vitiligo-through-melanocyte-stem-cell-mobilization
#7
REVIEW
Stanca A Birlea, Gertrude-E Costin, Dennis R Roop, David A Norris
Vitiligo is the most frequent human pigmentary disorder, characterized by progressive autoimmune destruction of mature epidermal melanocytes. Of the current treatments offering partial and temporary relief, ultraviolet (UV) light is the most effective, coordinating an intricate network of keratinocyte and melanocyte factors that control numerous cellular and molecular signaling pathways. This UV-activated process is a classic example of regenerative medicine, inducing functional melanocyte stem cell populations in the hair follicle to divide, migrate, and differentiate into mature melanocytes that regenerate the epidermis through a complex process involving melanocytes and other cell lineages in the skin...
December 28, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27993971/the-cd9-cd81-and-cd151-ec2-domains-bind-to-the-classical-rgd-binding-site-of-integrin-%C3%AE-v%C3%AE-3
#8
Jessica Yu, Chia-Ying Lee, Chun Austin Changou, Dora M Cedano-Prieto, Yoko K Takada, Yoshikazu Takada
Tetraspanins play important roles in normal (e.g., cell adhesion, motility, activation, and proliferation), and pathological conditions (e.g., metastasis and viral infection). Tetraspanins interact with integrins and regulate integrin functions, but the specifics of tetraspanin-integrin interaction are unclear. Using co-immunoprecipitation with integrins as a sole method to detect interaction between integrins and full-length tetraspanins, it has been proposed that the variable region (helices D and E) of the extracellular-2 (EC2) of tetraspanins laterally associate with non-ligand-binding site of integrins...
December 19, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27974566/cd63-regulates-epstein-barr-virus-lmp1-exosomal-packaging-enhancement-of-vesicle-production-and-non-canonical-nf-%C3%AE%C2%BAb-signaling
#9
Stephanie N Hurwitz, Dingani Nkosi, Meghan M Conlon, Sara B York, Xia Liu, Deanna C Tremblay, David G Meckes
: Latent membrane protein 1 (LMP1) is an Epstein-Barr virus (EBV) encoded oncoprotein that is packaged into small extracellular vesicles (EVs) called exosomes. Trafficking of LMP1 into multivesicular bodies (MVBs) alters the content and function of exosomes. LMP1-modified exosomes enhance the growth, migration, and invasion of malignant cells, demonstrating the capacity to manipulate the tumor microenvironment and enhance the progression of EBV-associated cancers. Despite the growing evidence surrounding the significance of LMP1-modified exosomes in cancer, very little is understood about the mechanisms that orchestrate LMP1 incorporation into these vesicles...
December 14, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27930836/hepatitis-c-virus-infection-propagates-through-interactions-between-syndecan-1-and-cd81-and-impacts-the-hepatocyte-glycocalyx
#10
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, in particular Syndecan-1, followed by recognition of the tetraspanin CD81 and other receptors. Heparan sulfate proteoglycans 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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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 the melanoma cell surface. GPR56 activation by immobilized CG4 monoclonal antibody facilitates N-terminal fragment dissociation in a CD9/CD81-dependent manner specifically inducing IL-6 production, which promotes cell migration and invasion...
November 3, 2016: Journal of Investigative Dermatology
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