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https://www.readbyqxmd.com/read/29458060/crim1-is-required-for-maintenance-of-the-ocular-lens-epithelium
#1
Oliver H Tam, David Pennisi, Lorine Wilkinson, Melissa H Little, Fatima Wazin, Victor L Wan, Frank J Lovicu
The development and growth of the vertebrate ocular lens is dependent on the regulated proliferation of an anterior monolayer of epithelial cells, and their subsequent differentiation into elongate fiber cells. The growth factor rich ocular media that bathes the lens mediates these cellular processes, and their respective intracellular signaling pathways are in turn regulated to ensure that the proper lens architecture is maintained. Recent studies have proposed that Cysteine Rich Motor Neuron 1 (Crim1), a transmembrane protein involved in organogenesis of many tissues, might influence cell adhesion, polarity and proliferation in the lens by regulating integrin-signaling...
February 16, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29458046/bmp-2-induces-angiogenesis-by-provoking-integrin-%C3%AE-6-expression-in-human-endothelial-progenitor-cells
#2
Wei-Cheng Chen, Ching-Hu Chung, Yung-Chang Lu, Min-Huan Wu, Po-Hsun Chou, Juei-Yu Yen, Yu-Wei Lai, Guo-Shou Wang, Shih-Chia Liu, Jen-Kun Cheng, Yih-Jer Wu, Hung-I Yeh, Li-Yu Wang, Shih-Wei Wang
Bone morphogenetic proteins-2 (BMP-2) is a multifunctional cytokine, capable of governing several cellular functions, including proliferation, motility, differentiation, and angiogenesis. Circulating endothelial progenitor cells (EPCs) have been shown to facilitate tissue repair, postnatal neovascularization, and tumor associated angiogenesis. Nevertheless, the impact of BMP-2 on angiogenesis of human EPCs has largely remained a mystery. In this study, we found that BMP-2 promoted cell migration and tube formation of EPCs in a concentration-dependent manner, indicating BMP-2 induced in vitro angiogenesis in human EPCs...
February 16, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29455614/ddr1-a-major-player-in-renal-diseases
#3
Aude Dorison, Christos Chantziantoniou
Discoidin Domain Receptor 1 (DDR1) belongs to a family of two non-integrin collagen receptors, DDR1 and DDR2, which display a tyrosine kinase activity. DDR1 has been widely studied in different kind of pathologies including chronic kidney diseases (CKD). The aims of this commentary are 1. to review the existing information about DDR1 expression in healthy and diseased kidney, 2. to comment the data highlighting DDR1 as a major actor in CKD, 3. to suggest areas of research which require further investigation to better characterize the signaling pathways regulating DDR1 role in CKD...
February 19, 2018: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/29454158/polyisocyanopeptide-hydrogels-a-novel-thermo-responsive-hydrogel-supporting-pre-vascularization-and-the-development-of-organotypic-structures
#4
Jakub Zimoch, Joan Simó Padial, Agnes S Klar, Queralt Vallmajo-Martin, Martin Meuli, Thomas Biedermann, Christopher J Wilson, Alan Rowan, Ernst Reichmann
Molecular and mechanical interactions with the 3D extracellular matrix are essential for cell functions such as survival, proliferation, migration, and differentiation. Thermo-responsive biomimetic polyisocyanopeptide (PIC) hydrogels are promising new candidates for 3D cell, tissue, and organ cultures. This is a synthetic, thermo-responsive and stress-stiffening material synthesized via polymerization of the corresponding monomers using a nickel perchlorate as a catalyst. It can be tailored to meet various demands of cells by modulating its stiffness and through the decoration of the polymer with short GRGDS peptides using copper free click chemistry...
February 14, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29453458/il-2-inducible-kinase-itk-is-critical-for-hiv-1-infection-of-jurkat-t-cells
#5
Anika Hain, Melanie Krämer, René M Linka, Saeideh Nakhaei-Rad, Mohammad Reza Ahmadian, Dieter Häussinger, Arndt Borkhardt, Carsten Münk
Successful replication of Human immunodeficiency virus (HIV)-1 depends on the expression of various cellular host factors, such as the interleukin-2 inducible T-cell kinase (ITK), a member of the protein family of TEC-tyrosine kinases. ITK is selectively expressed in T-cells and coordinates signaling pathways downstream of the T-cell receptor and chemokine receptors, including PLC-1 activation, Ca 2+ -release, transcription factor mobilization, and actin rearrangements. The exact role of ITK during HIV-1 infection is still unknown...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453316/brd1-mediated-acetylation-promotes-integrin-%C3%AE-v-gene-expression-via-interaction-with-sulfatide
#6
Qian Qian Cai, Yi Wei Dong, Bing Qi, Xiao-Ting Shao, Rong Wang, Zhong Yi Chen, Bao Mei He, Xing Zhong Wu
Integrin αV (ITGAV) gene expression is often dysregulated in cancers especially in hepatocellular carcinoma (HCC); however, the mechanism of regulation is poorly understood. Here, it is demonstrated that sulfatide activated integrin αV gene transcription, through histone H3K9/14 acetylation at the promoter, and high integrin αV expression are closely associated with poor prognosis. To elucidate the mechanism of regulation of acetylation, sulfatide-bound proteins were screened by mass spectrometry (MS), and BRD1 (bromodomain containing protein 1) was identified as an interacting protein that also co-localized with sulfatide in HCC cells...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29453194/comparison-of-generic-fluorescent-markers-for-detection-of-extracellular-vesicles-by-flow-cytometry
#7
Leonie de Rond, Edwin van der Pol, Chi M Hau, Zoltan Varga, Auguste Sturk, Ton G van Leeuwen, Rienk Nieuwland, Frank A W Coumans
BACKGROUND: Extracellular vesicles (EVs) in biofluids are potential biomarkers of disease. To explore the clinical relevance of EVs, a specific generic EV marker would be useful, one that does not require antibodies and binds to all EVs. Here we evaluated 5 commonly used generic markers for flow cytometry. METHODS: Flow cytometry (A60-Micro, Apogee) was used to evaluate the ability of the generic EV markers calcein acetoxymethyl ester, calcein acetoxymethyl ester violet, carboxyfluorescein succinimidyl ester (CFSE), 4-(2-[6-(dioctylamino)-2-naphthalenyl]ethenyl)-1-(3-sulfopropyl)pyridinium (di-8-ANEPPS), and lactadherin to stain EVs from MCF7 human breast adenocarcinoma cell line-conditioned culture medium [epithelial cell adhesion molecule positive (EpCAM + )] or platelet EVs from human plasma [integrin β3 positive (CD61 + )]...
February 16, 2018: Clinical Chemistry
https://www.readbyqxmd.com/read/29449447/tracers-for-fluorescence-guided-surgery-how-elongation-of-the-polymethine-chain-in-cyanine-dyes-alters-the-pharmacokinetics-of-a-bimodal-c-rgdyk-tracer
#8
Tessa Buckle, Danny M van Willigen, Silvia J Spa, Albertus W Hensbergen, Steffen van der Wal, Clarize M de Korne, Mick M Welling, Henk G van der Poel, James C H Hardwick, Fijs W B van Leeuwen
Objectives: The potential of (receptor-mediated) fluorescence-based image-guided surgery tracers is generally linked to the near-infrared emission profile and good manufacturing production (GMP) availability of fluorescent dyes. Surprisingly, little is known about the critical interaction between the structural composition of the dye and the pharmacokinetics of the tracers. In this study, a bimodal/hybrid tracer design was used to systematically and quantitatively evaluate the influence of elongation of the polymethine chain in a fluorescent cyanine (Cy) dye on the imaging potential of a targeted (RGD-based) tracer...
February 15, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29446689/platelets-and-vascular-integrity
#9
Carsten Deppermann
Platelets patrol the vasculature and adhere at sites of vascular damage after trauma to limit blood loss. In recent years, however, it has become clear that platelets also contribute to pathophysiologic processes such as thrombosis, atherosclerosis, stroke, sepsis and many more. An exciting new role for them is in non-classical hemostasis to prevent bleeding in the inflamed vasculature. Recent studies suggest that GPVI, CLEC-2, integrin αIIbβ3 (GPIIb/IIIa), and the content of platelet α- and dense granules are important players in this process...
February 15, 2018: Platelets
https://www.readbyqxmd.com/read/29446228/integrins-promote-axonal-regeneration-after-injury-of-the-nervous-system
#10
Bart Nieuwenhuis, Barbara Haenzi, Melissa R Andrews, Joost Verhaagen, James W Fawcett
Integrins are cell surface receptors that form the link between extracellular matrix molecules of the cell environment and internal cell signalling and the cytoskeleton. They are involved in several processes, e.g. adhesion and migration during development and repair. This review focuses on the role of integrins in axonal regeneration. Integrins participate in spontaneous axonal regeneration in the peripheral nervous system through binding to various ligands that either inhibit or enhance their activation and signalling...
February 15, 2018: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/29444939/single-cell-analysis-of-the-impact-of-host-cell-heterogeneity-on-infection-with-foot-and-mouth-disease-virus
#11
Xiu Xin, Hailong Wang, Lingling Han, Mingzhen Wang, Hui Fang, Yao Hao, Jiadai Li, Hu Zhang, Congyi Zheng, Chao Shen
Viral infection and replication are affected by host-cell heterogeneity, but the mechanisms underlying the effects remain unclear. Using single-cell analysis, we investigated the effects of host-cell heterogeneity, including cell size, inclusion, and cell cycle, on foot and mouth disease virus (FMDV) infection (acute and persistent infections) and replication. We detected variable viral genome replication levels in FMDV-infected cells. Larger cells and cells with a greater number of inclusions generated more viral RNA copies, viral protein, and a higher proportion of infectious cells...
February 14, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29444440/measuring-integrin-conformational-change-on-the-cell-surface-with-super-resolution-microscopy
#12
Travis I Moore, Jesse Aaron, Teng-Leong Chew, Timothy A Springer
We use super-resolution interferometric photoactivation and localization microscopy (iPALM) and a constrained photoactivatable fluorescent protein integrin fusion to measure the displacement of the head of integrin lymphocyte function-associated 1 (LFA-1) resulting from integrin conformational change on the cell surface. We demonstrate that the distance of the LFA-1 head increases substantially between basal and ligand-engaged conformations, which can only be explained at the molecular level by integrin extension...
February 13, 2018: Cell Reports
https://www.readbyqxmd.com/read/29444419/pak1-kinase-maintains-apical-membrane-identity-in-epithelia
#13
Mario Aguilar-Aragon, Ahmed Elbediwy, Valentina Foglizzo, Georgina C Fletcher, Vivian S W Li, Barry J Thompson
Epithelial cells are polarized along their apical-basal axis by the action of the small GTPase Cdc42, which is known to activate the aPKC kinase at the apical domain. However, loss of aPKC kinase activity was reported to have only mild effects on epithelial cell polarity. Here, we show that Cdc42 also activates a second kinase, Pak1, to specify apical domain identity in Drosophila and mammalian epithelia. aPKC and Pak1 phosphorylate an overlapping set of polarity substrates in kinase assays. Inactivating both aPKC kinase activity and the Pak1 kinase leads to a complete loss of epithelial polarity and morphology, with cells losing markers of apical polarization such as Crumbs, Par3/Bazooka, or ZO-1...
February 13, 2018: Cell Reports
https://www.readbyqxmd.com/read/29443958/tissue-stiffening-coordinates-morphogenesis-by-triggering-collective-cell-migration-in-vivo
#14
Elias H Barriga, Kristian Franze, Guillaume Charras, Roberto Mayor
Collective cell migration is essential for morphogenesis, tissue remodelling and cancer invasion. In vivo, groups of cells move in an orchestrated way through tissues. This movement involves mechanical as well as molecular interactions between cells and their environment. While the role of molecular signals in collective cell migration is comparatively well understood, how tissue mechanics influence collective cell migration in vivo remains unknown. Here we investigated the importance of mechanical cues in the collective migration of the Xenopus laevis neural crest cells, an embryonic cell population whose migratory behaviour has been likened to cancer invasion...
February 14, 2018: Nature
https://www.readbyqxmd.com/read/29443896/dexamethasone-mediated-upregulation-of-calreticulin-inhibits-primary-human-glioblastoma-dispersal-ex-vivo
#15
Mohan Nair, Juan Romero, Aria Mahtabfar, Ahmed M Meleis, Ramsey A Foty, Siobhan A Corbett
Dispersal of Glioblastoma (GBM) renders localized therapy ineffective and is a major cause of recurrence. Previous studies have demonstrated that Dexamethasone (Dex), a drug currently used to treat brain tumor-related edema, can also significantly reduce dispersal of human primary GBM cells from neurospheres. It does so by triggering α5 integrin activity, leading to restoration of fibronectin matrix assembly (FNMA), increased neurosphere cohesion, and reduction of neurosphere dispersal velocity (DV). How Dex specifically activates α5 integrin in these GBM lines is unknown...
February 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29441976/calreticulin-a-potential-anti-cancer-therapeutic-target
#16
Jing Sun, Hongxiang Mu, Keren Dai, Lan Yi
Calreticulin (CRT) is an endoplasmic reticulum luminal calcium-binding protein with multiple cellular functions, including intracellular Ca2+ homeostasis, oxidative stress responses, and lectin binding. CRT can also modulate cell adhesion, cell-cell interactions, migration, phagocytosis, integrin-dependent Ca2+ signaling, and immune responses, and plays an important role in cellular proliferation, differentiation, and apoptosis. Given these roles, it is not surprising that CRT function has important implications in health and disease...
September 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29441061/profiling-of-human-molecular-pathways-affected-by-retrotransposons-at-the-level-of-regulation-by-transcription-factor-proteins
#17
Daniil Nikitin, Dmitry Penzar, Andrew Garazha, Maxim Sorokin, Victor Tkachev, Nicolas Borisov, Alexander Poltorak, Vladimir Prassolov, Anton A Buzdin
Endogenous retroviruses and retrotransposons also termed retroelements (REs) are mobile genetic elements that were active until recently in human genome evolution. REs regulate gene expression by actively reshaping chromatin structure or by directly providing transcription factor binding sites (TFBSs). We aimed to identify molecular processes most deeply impacted by the REs in human cells at the level of TFBS regulation. By using ENCODE data, we identified ~2 million TFBS overlapping with putatively regulation-competent human REs located in 5-kb gene promoter neighborhood (~17% of all TFBS in promoter neighborhoods; ~9% of all RE-linked TFBS)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29440721/salt-bridge-modulates-differential-calcium-mediated-ligand-binding-to-integrin-%C3%AE-1-and-%C3%AE-2-i-domains
#18
Kyle L Brown, Surajit Banerjee, Andrew Feigley, Hanna Abe, Timothy S Blackwell, Ambra Pozzi, Billy G Hudson, Roy Zent
Integrins are transmembrane cell-extracellular matrix adhesion receptors that impact many cellular functions. A subgroup of integrins contain an inserted (I) domain within the α-subunits (αI) that mediate ligand recognition where function is contingent on binding a divalent cation at the metal ion dependent adhesion site (MIDAS). Ca2+is reported to promote α1I but inhibit α2I ligand binding. We co-crystallized individual I-domains with MIDAS-bound Ca2+and report structures at 1.4 and 2.15 Å resolution, respectively...
February 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29440271/phosphorylated-immunoreceptor-tyrosine-based-activation-motifs-and-integrin-cytoplasmic-domains-activate-spleen-tyrosine-kinase-via-distinct-mechanisms
#19
Lina Antenucci, Vesa P Hytönen, Jari Ylänne
Spleen tyrosine kinase (Syk) is involved in cellular adhesion and also in the activation and development of hematopoietic cells. Syk activation induced by genomic rearrangement has been linked to certain T-cell lymphomas, and Syk inhibitors have been shown to prolong survival of patients with B-cell lineage malignancies. Syk is activated either by its interaction with a double-phosphorylated Immunoreceptor Tyrosine-based Activation Motif (pITAM), which induces rearrangements in the Syk structure, or by the phosphorylation of specific tyrosine residues...
February 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29440263/mechanical-stress-regulates-insulin-sensitivity-through-integrin-dependent-control-of-insulin-receptor-localization
#20
Jung Kim, David Bilder, Thomas P Neufeld
Insulin resistance, the failure to activate insulin signaling in the presence of ligand, leads to metabolic diseases, including type 2 diabetes. Physical activity and mechanical stress have been shown to protect against insulin resistance, but the molecular mechanisms remain unclear. Here, we address this relationship in the Drosophila larval fat body, an insulin-sensitive organ analogous to vertebrate adipose tissue and livers. We found that insulin signaling in Drosophila fat body cells is abolished in the absence of physical activity and mechanical stress even when excess insulin is present...
January 15, 2018: Genes & Development
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