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Cortactin

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https://www.readbyqxmd.com/read/28441759/synaptic-homeostasis-and-its-immunological-disturbance-in-neuromuscular-junction-disorders
#1
REVIEW
Masaharu Takamori
In the neuromuscular junction, postsynaptic nicotinic acetylcholine receptor (nAChR) clustering, trans-synaptic communication and synaptic stabilization are modulated by the molecular mechanisms underlying synaptic plasticity. The synaptic functions are based presynaptically on the active zone architecture, synaptic vesicle proteins, Ca(2+) channels and synaptic vesicle recycling. Postsynaptically, they are based on rapsyn-anchored nAChR clusters, localized sensitivity to ACh, and synaptic stabilization via linkage to the extracellular matrix so as to be precisely opposed to the nerve terminal...
April 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28428256/regulation-of-lung-endothelial-permeability-and-inflammatory-responses-by-prostaglandin-a2-role-of-ep4-receptor
#2
Tomomi Ohmura, Yufeng Tian, Nicolene Sarich, Yunbo Ke, Angelo Meliton, Alok S Shah, Katrin Andreasson, Konstantin G Birukov, Anna A Birukova
A role of prostaglandin A2 (PGA2) in modulation of vascular endothelial function remains unknown. We investigated effects of PGA2 on pulmonary endothelial cell (EC) permeability and inflammatory activation and identified a receptor mediating these effects. PGA2 enhanced the EC barrier and protected against barrier dysfunction caused by vasoactive peptide thrombin and proinflammatory bacterial wall lipopolysacharide (LPS). Receptor screening using pharmacologic and molecular inhibitory approaches identified EP4 as a novel PGA2 receptor...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28423567/cxcr1-2-pathways-in-paclitaxel-induced-neuropathic-pain
#3
Brandolini Laura, Benedetti Elisabetta, Ruffini Pier Adelchi, Russo Roberto, Cristiano Loredana, Antonosante Andrea, d'Angelo Michele, Castelli Vanessa, Giordano Antonio, Allegretti Marcello, Cimini Annamaria
Chemotherapy-induced peripheral neuropathy (CIPN) is a type of neuropathic pain that represents a frequent and serious consequence of chemotherapy agents. Over the last years, significant progress has been achieved in elucidating the underlying pathogenesis of CIPN. The interference of taxanes with microtubule has been proposed as a mechanism that leads to altered axonal transport and to permanent neurological damages. The inflammatory process activated by chemotherapeutic agents has been considered as a potential trigger of nociceptive process in CIPN...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419476/cortactin-a-lyn-substrate-is-a-checkpoint-molecule-at-the-intersection-of-bcr-and-cxcr4-signalling-pathway-in-chronic-lymphocytic-leukaemia-cells
#4
Veronica Martini, Cristina Gattazzo, Federica Frezzato, Valentina Trimarco, Marco Pizzi, Giorgia Chiodin, Filippo Severin, Edoardo Scomazzon, Vincenza Guzzardo, Deborah Saraggi, Flavia Raggi, Leonardo Martinello, Monica Facco, Andrea Visentin, Francesco Piazza, Anna Maria Brunati, Gianpietro Semenzato, Livio Trentin
Cortactin (CTTN) is a substrate of the Src kinase Lyn that is known to play an actin cytoskeletal regulatory role involved in cell migration and cancer progression following its phosphorylation at Y421. We recently demonstrated that Cortactin is overexpressed in patients with chronic lymphocytic leukaemia (CLL). This work was aimed at defining the functional role of Cortactin in these patients. We found that Cortactin is variably expressed in CLL patients both in the peripheral blood and lymph nodes and that its expression correlates with the release of matrix metalloproteinase 9 (MMP-9) and the motility of neoplastic cells...
April 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28416666/drebrin-restricts-rotavirus-entry-by-inhibiting-dynamin-mediated-endocytosis
#5
Bin Li, Siyuan Ding, Ningguo Feng, Nancie Mooney, Yaw Shin Ooi, Lili Ren, Jonathan Diep, Marcus R Kelly, Linda L Yasukawa, John T Patton, Hiroyuki Yamazaki, Tomoaki Shirao, Peter K Jackson, Harry B Greenberg
Despite the wide administration of several effective vaccines, rotavirus (RV) remains the single most important etiological agent of severe diarrhea in infants and young children worldwide, with an annual mortality of over 200,000 people. RV attachment and internalization into target cells is mediated by its outer capsid protein VP4. To better understand the molecular details of RV entry, we performed tandem affinity purification coupled with high-resolution mass spectrometry to map the host proteins that interact with VP4...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28404950/high-expression-of-ptbp1-promote-invasion-of-colorectal-cancer-by-alternative-splicing-of-cortactin
#6
Zhi-Na Wang, Dan Liu, Bin Yin, Wen-Yi Ju, Hui-Zhong Qiu, Yi Xiao, Yuan-Jia Chen, Xiao-Zhong Peng, Chong-Mei Lu
Polypyrimidine tract-binding protein 1 (PTBP1) involving in almost all steps of mRNA regulation including alternative splicing metabolism during tumorigenesis due to its RNA-binding activity. Initially, we found that high expressed PTBP1 and poor prognosis was interrelated in colorectal cancer (CRC) patients with stages II and III CRC, which widely different in prognosis and treatment, by immunohistochemistry. PTBP1 was also upregulated in colon cancer cell lines. In our study, knockdown of PTBP1 by siRNA transfection decreased cell proliferation and invasion in vitro...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28364518/interaction-between-ezrin-and-cortactin-in-promoting-epithelial-to-mesenchymal-transition-in-breast-cancer-cells
#7
Jing He, Ge Ma, Jiayi Qian, Yichao Zhu, Mengdi Liang, Na Yao, Qiang Ding, Lin Chen, Xiaoan Liu, Tiansong Xia, Shui Wang
BACKGROUND Epithelial to mesenchymal transition (EMT) contributes to metastases in various types of tumors, and is also the key step in the breast cancer metastatic cascade. In our previous study, a mouse model containing human-derived normal breast tissue was established and allowed EMT/MET process of human breast cancer cells to be mimicked in a humanized mammary microenvironment. MATERIAL AND METHODS Two-dimensional electrophoresis (2-DE) and mass spectrometry were used to detect different proteins between parental MDA-MB-231 and its variant sub-line obtained from tumors grown in transplanted normal human breast tissue (MDA-MB-231br)...
April 1, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28356423/phosphorylated-cortactin-recruits-vav2-guanine-nucleotide-exchange-factor-to-activate-rac3-and-promote-invadopodial-function-in-invasive-breast-cancer-cells
#8
Brian J Rosenberg, Hava Gil-Henn, Christopher C Mader, Tiffany Halo, Taofei Yin, John Condeelis, Kazuya Machida, Yi I Wu, Anthony J Koleske
Breast carcinoma cells use specialized, actin-rich protrusions called invadopodia to degrade and invade through the extracellular matrix. Phosphorylation of the actin nucleation promoting factor and actin stabilizing protein cortactin downstream of the EGF receptor-Src-Arg kinase cascade is known to be a critical trigger for invadopodium maturation and subsequent cell invasion in breast cancer cells. The functions of cortactin phosphorylation in this process, however, are not completely understood. We identified the Rho-family guanine nucleotide exchange factor (GEF) Vav2 in a comprehensive screen for human SH2 domains that bind selectively to phosphorylated cortactin...
March 29, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28341841/regulation-of-membrane-ruffling-by-polarized-stim1-and-orai1-in-cortactin-rich-domains
#9
Aida M Lopez-Guerrero, Patricia Tomas-Martin, Carlos Pascual-Caro, Thomas Macartney, Alejandro Rojas-Fernandez, Graeme Ball, Dario R Alessi, Eulalia Pozo-Guisado, Francisco Javier Martin-Romero
Cell motility and migration requires the reorganization of the cortical cytoskeleton at the leading edge of cells and extracellular Ca(2+) entry is essential for this reorganization. However the molecular nature of the regulators of this pathway is unknown. This work contributes to understanding the role of STIM1 and ORAI1 in the promotion of membrane ruffling by showing that phospho-STIM1 localizes at the leading edge of cells, and that both phospho-STIM1 and ORAI1 co-localize with cortactin (CTTN), a regulator of the cytoskeleton at membrane ruffling areas...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28335271/distribution-of-iron-oxide-core-titanium-dioxide-shell-nanoparticles-in-vx2-tumor-bearing-rabbits-introduced-by-two-different-delivery-modalities
#10
Tamer Refaat, Derek West, Samar El Achy, Vamsi Parimi, Jasmine May, Lun Xin, Kathleen R Harris, William Liu, Michael Beau Wanzer, Lydia Finney, Evan Maxey, Stefan Vogt, Reed A Omary, Daniele Procissi, Andrew C Larson, Tatjana Paunesku, Gayle E Woloschak
This work compares intravenous (IV) versus fluoroscopy-guided transarterial intra-catheter (IC) delivery of iron oxide core-titanium dioxide shell nanoparticles (NPs) in vivo in VX2 model of liver cancer in rabbits. NPs coated with glucose and decorated with a peptide sequence from cortactin were administered to animals with developed VX2 liver cancer. Two hours after NPs delivery tumors, normal liver, kidney, lung and spleen tissues were harvested and used for a series on histological and elemental analysis tests...
August 3, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28306714/reconstruction-and-signal-propagation-analysis-of-the-syk-signaling-network-in-breast-cancer-cells
#11
Aurélien Naldi, Romain M Larive, Urszula Czerwinska, Serge Urbach, Philippe Montcourrier, Christian Roy, Jérôme Solassol, Gilles Freiss, Peter J Coopman, Ovidiu Radulescu
The ability to build in-depth cell signaling networks from vast experimental data is a key objective of computational biology. The spleen tyrosine kinase (Syk) protein, a well-characterized key player in immune cell signaling, was surprisingly first shown by our group to exhibit an onco-suppressive function in mammary epithelial cells and corroborated by many other studies, but the molecular mechanisms of this function remain largely unsolved. Based on existing proteomic data, we report here the generation of an interaction-based network of signaling pathways controlled by Syk in breast cancer cells...
March 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28293874/diversity-of-actin-architecture-in-human-osteoclasts-network-of-curved-and-branched-actin-supporting-cell-shape-and-intercellular-micrometer-level-tubes
#12
Paula Pennanen, Maria Helena Alanne, Elnaz Fazeli, Takahiro Deguchi, Tuomas Näreoja, Sirkku Peltonen, Juha Peltonen
Osteoclasts are multinucleated bone-resorbing cells with a dynamic actin cytoskeleton. Osteoclasts are derived from circulating mononuclear precursors. Confocal and stimulated emission depletion (STED) super-resolution microscopy was used to investigate peripheral blood-derived human osteoclasts cultured on glass surfaces. STED and confocal microscopy demonstrated that the actin was curved and branched, for instance, in the vicinity of membrane ruffles. The overall architecture of the curved actin network extended from the podosomes to the top of the cell...
March 14, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28287395/p27-kip1-promotes-invadopodia-turnover-and-invasion-through-the-regulation-of-the-pak1-cortactin-pathway
#13
Pauline Jeannot, Ada Nowosad, Renaud T Perchey, Caroline Callot, Evangeline Bennana, Takanori Katsube, Patrick Mayeux, François Guillonneau, Stéphane Manenti, Arnaud Besson
p27(Kip1) (p27) is a cyclin-CDK inhibitor and negative regulator of cell proliferation. p27 also controls other cellular processes including migration and cytoplasmic p27 can act as an oncogene. Furthermore, cytoplasmic p27 promotes invasion and metastasis, in part by promoting epithelial to mesenchymal transition. Herein, we find that p27 promotes cell invasion by binding to and regulating the activity of Cortactin, a critical regulator of invadopodia formation. p27 localizes to invadopodia and limits their number and activity...
March 13, 2017: ELife
https://www.readbyqxmd.com/read/28235780/inhibitory-cortactin-nanobodies-delineate-the-role-of-nta-and-sh3-domain-specific-functions-during-invadopodium-formation-and-cancer-cell-invasion
#14
Laurence Bertier, Ciska Boucherie, Olivier Zwaenepoel, Berlinda Vanloo, Marleen Van Troys, Isabel Van Audenhove, Jan Gettemans
Cancer cells exploit different strategies to escape from the primary tumor, gain access to the circulation, disseminate throughout the body, and form metastases, the leading cause of death by cancer. Invadopodia, proteolytically active plasma membrane extensions, are essential in this escape mechanism. Cortactin is involved in every phase of invadopodia formation, and its overexpression is associated with increased invadopodia formation, extracellular matrix degradation, and cancer cell invasion. To analyze endogenous cortactin domain function in these processes, we characterized the effects of nanobodies that are specific for the N-terminal acidic domain of cortactin and expected to target small epitopes within this domain...
February 24, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28166391/lactosamine-based-derivatives-as-tools-to-delineate-the-biological-functions-of-galectins-application-to-skin-tissue-repair
#15
Johann Dion, Frédérique Deshayes, Nataliya Storozhylova, Tamara Advedissian, Annie Lambert, Mireille Viguier, Charles Tellier, Christophe Dussouy, Françoise Poirier, Cyrille Grandjean
Galectins have been recognized as potential novel therapeutic targets for the numerous fundamental biological processes in which they are involved. Galectins are key players in homeostasis, and as such their expression and function are finely tuned in vivo. Thus, their modes of action are complex and remain largely unexplored, partly because of the lack of dedicated tools. We thus designed galectin inhibitors from a lactosamine core, functionalized at key C2 and C3' positions by aromatic substituents to ensure both high affinity and selectivity, and equipped with a spacer that can be modified on demand to further modulate their physico-chemical properties...
February 6, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28131549/cortactin-and-phosphorylated-cortactin-tyr-466-expression-in-temporal-bone-carcinoma
#16
Gino Marioni, Elisabetta Zanoletti, Antonio Mazzoni, Andrea Gianatti, Elisa Valentini, Laura Girasoli, Martina Guariento, Luciano Giacomelli, Alessandro Martini, Stella Blandamura
PURPOSE: Cortactin is a multidomain protein engaged in several cellular mechanisms involving actin assembly and cytoskeletal arrangement. Cortactin overexpression in several malignancies has been associated with increased cell migration, invasion, and metastatic potential. Cortactin needs to be activated by tyrosine or serine/threonine phosphorylation. The role of cortactin and phosphorylated cortactin (residue tyr(466)) was investigated in temporal bone squamous cell carcinoma (TBSCC)...
March 2017: American Journal of Otolaryngology
https://www.readbyqxmd.com/read/28126411/perfluorooctanoic-acid-affects-endocytosis-involving-clathrin-light-chain-a-and-microrna-133b-3p-in-mouse-testes
#17
Yin Lu, Jianshe Wang, Xuejiang Guo, Shengmin Yan, Jiayin Dai
Perfluorooctanoic acid (PFOA) is an abundant perfluoroalkyl substance widely applied in industrial and consumer products. Among its potential health hazards, testicular toxicity is of major concern. To explore the potential effect of miRNA on post-translational regulation after PFOA exposure, changes in miRNAs were detected via miRNA array. Seventeen miRNAs were differentially expressed (eight upregulated, nine downregulated) in male mouse testes after exposure to 5mg/kg/d of PFOA for 28d (>1.5-fold and P<0...
March 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28123080/cortactin-is-a-regulator-of-activity-dependent-synaptic-plasticity-controlled-by-wingless
#18
Daniel Alicea, Marizabeth Perez, Carolina Maldonado, Carihann Dominicci-Cotto, Bruno Marie
Major signaling molecules initially characterized as key early developmental regulators are also essential for the plasticity of the nervous system. Previously, the Wingless (Wg)/Wnt pathway was shown to underlie the structural and electrophysiological changes during activity-dependent synaptic plasticity at the Drosophila neuromuscular junction. A challenge remains to understand how this signal mediates the cellular changes underlying this plasticity. Here, we focus on the actin regulator Cortactin, a major organizer of protrusion, membrane mobility, and invasiveness, and define its new role in synaptic plasticity...
February 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28122813/hs1-deficiency-impairs-neutrophil-recruitment-in-vivo-and-activation-of-the-small-gtpases-rac1-and-rap1
#19
Joanna Latasiewicz, Annette Artz, Ding Jing, Mariana Pacheco Blanco, Silke M Currie, Martha Velázquez Avila, Michael Schnoor, Dietmar Vestweber
Neutrophil extravasation is a critical step of the innate immune system's response to inflammation. This multistep process is tightly regulated by adhesion and signaling molecules in the endothelium and neutrophils. Activation of the β2 integrin LFA-1 is critical for adhesion of leukocytes to postcapillary venules. This step requires coordinated activation of signaling pathways in chemokine-stimulated neutrophils, including GTPase activation and cytoskeletal remodeling, leading to conformational changes in LFA-1...
January 25, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28120846/cortactin-deficiency-causes-increased-rhoa-rock1-dependent-actomyosin-contractility-intestinal-epithelial-barrier-dysfunction-and-disproportionately-severe-dss-induced-colitis
#20
A F Citalán-Madrid, H Vargas-Robles, A García-Ponce, M Shibayama, A Betanzos, P Nava, C Salinas-Lara, K Rottner, R Mennigen, M Schnoor
The intestinal epithelium constitutes a first line of defense of the innate immune system. Epithelial dysfunction is a hallmark of intestinal disorders such as inflammatory bowel diseases (IBDs). The actin cytoskeleton controls epithelial barrier integrity but the function of actin regulators such as cortactin is poorly understood. Given that cortactin controls endothelial permeability, we hypothesized that cortactin is also important for epithelial barrier regulation. We found increased permeability in the colon of cortactin-KO mice that was accompanied by reduced levels of ZO-1, claudin-1, and E-cadherin...
January 25, 2017: Mucosal Immunology
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