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Nascent adhesion

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https://www.readbyqxmd.com/read/28459445/egfr-and-her2-activate-rigidity-sensing-only-on-rigid-matrices
#1
Mayur Saxena, Shuaimin Liu, Bo Yang, Cynthia Hajal, Rishita Changede, Junqiang Hu, Haguy Wolfenson, James Hone, Michael P Sheetz
Epidermal growth factor receptor (EGFR) interacts with integrins during cell spreading and motility, but little is known about the role of EGFR in these mechanosensing processes. Here we show, using two different cell lines, that in serum- and EGF-free conditions, EGFR or HER2 activity increase spreading and rigidity-sensing contractions on rigid, but not soft, substrates. Contractions peak after 15-20 min, but diminish by tenfold after 4 h. Addition of EGF at that point increases spreading and contractions, but this can be blocked by myosin-II inhibition...
May 1, 2017: Nature Materials
https://www.readbyqxmd.com/read/28448919/mechanochemical-mechanism-of-integrin-clustering-modulated-by-nanoscale-ligand-spacing-and-rigidity-of-extracellular-substrates
#2
Jing Yu, Jianyong Huang, John A Jansen, Chunyang Xiong, X Frank Walboomers
Experimental findings indicate that cell function and behavior such as cell growth, division, migration and differentiation, are subtly regulated via integrin-dependent cell adhesion. Cell adhesion is influenced by nanoscale ligand spacing and rigidity of extracellular substrates, as cell adhesion drops greatly when the ligand spacing is larger than ~60nm, and cell adhesion is stronger on stiff than soft substrates. However, how nanoscale ligand spacing and substrate stiffness jointly affect integrin clustering and hence nascent cell adhesion remains to be elucidated...
April 14, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/28388299/innovation-analysis-on-postgenomic-biomarkers-glycomics-for-chronic-diseases
#3
Eric Adua, Alyce Russell, Peter Roberts, Youxin Wang, Manshu Song, Wei Wang
Despite decades of investment in biomarker research, we still do not have robust and field-tested biomarkers for many chronic diseases so as to anticipate clinical outcomes and thus move toward personalized medicine. Biomarker innovations have tended to focus on genomics, but next-generation biomarkers from the nascent field of glycomics now offer fresh vistas for innovation in chronic disease biomarkers and systems diagnostics. Glycosylation, regarded as a complex enzymatic process where sugars (glycans) bind to proteins and lipids, affects many human biological functions, including cell signaling, adhesion, and motility...
April 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28318976/assembly-of-cns-nodes-of-ranvier-in-myelinated-nerves-is-promoted-by-the-axon-cytoskeleton
#4
Veronica Brivio, Catherine Faivre-Sarrailh, Elior Peles, Diane L Sherman, Peter J Brophy
Nodes of Ranvier in the axons of myelinated neurons are exemplars of the specialized cell surface domains typical of polarized cells. They are rich in voltage-gated sodium channels (Nav) and thus underpin rapid nerve impulse conduction in the vertebrate nervous system [1]. Although nodal proteins cluster in response to myelination, how myelin-forming glia influence nodal assembly is poorly understood. An axoglial adhesion complex comprising glial Neurofascin155 and axonal Caspr/Contactin flanks mature nodes [2]...
April 3, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28289087/reoxidation-of-the-thiol-disulfide-oxidoreductase-mdba-by-a-bacterial-vitamin-k-epoxide-reductase-in-the-biofilm-forming-actinobacterium-actinomyces-oris
#5
Truc Thanh Luong, Melissa E Reardon-Robinson, Sara D Siegel, Hung Ton-That
Posttranslocational protein folding in the Gram-positive biofilm-forming actinobacterium Actinomyces oris is mediated by a membrane-bound thiol-disulfide oxidoreductase named MdbA, which catalyzes oxidative folding of nascent polypeptides transported by the Sec translocon. Reoxidation of MdbA involves a bacterial vitamin K epoxide reductase (VKOR)-like protein that contains four cysteine residues, C93/C101 and C175/C178, with the latter forming a canonical CXXC thioredoxin-like motif; however, the mechanism of VKOR-mediated reoxidation of MdbA is not known...
May 15, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28255705/f%C3%A3-rster-resonance-energy-transfer-to-study-tcr-pmhc-interactions-in-the-immunological-synapse
#6
Gerhard J Schütz, Johannes B Huppa
T-cell antigen recognition is remarkably efficient: when scanning the surface of antigen-presenting cells (APCs), T-cells can detect the presence of just a few single antigenic peptide/MHCs (pMHCs), which are often vastly outnumbered by structurally similar non-stimulatory endogenous pMHCs (Irvine et al., Nature 419(6909):845-849, 2002; Purbhoo et al., Nat Immunol 5(5):524-530, 2004; Huang et al., Immunity 39(5):846-857, 2013). How T-cells achieve this is still enigmatic, in particular in view of the rather moderate affinity that TCRs typically exert for antigenic pMHCs, at least when measured in vitro (Davis et al...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28156030/er-to-golgi-blockade-of-nascent-desmosomal-cadherins-in-serca2-inhibited-keratinocytes-implications-for-darier-s-disease
#7
Ning Li, Moonhee Park, Shengxiang Xiao, Zhi Liu, Luis A Diaz
Darier's disease (DD) is an autosomal dominantly inherited skin disorder caused by mutations in sarco/endoplasmic reticulum Ca(2+) -ATPase 2 (SERCA2), a Ca(2+) pump that transports Ca(2+) from the cytosol to the endoplasmic reticulum (ER). Loss of desmosomes and keratinocyte cohesion is a characteristic feature of DD. Desmosomal cadherins (DC) are Ca(2+) -dependent transmembrane adhesion proteins of desmosomes, which are mislocalized in the lesional but not perilesional skin of DD. We show here that inhibition of SERCA2 by 2 distinct inhibitors results in accumulation of DC precursors in keratinocytes, indicating ER-to-Golgi transport of nascent DC is blocked...
April 2017: Traffic
https://www.readbyqxmd.com/read/28147641/monitoring-in-real-time-focal-adhesion-protein-dynamics-in-response-to-a-discrete-mechanical-stimulus
#8
Catalina von Bilderling, Martín Caldarola, Martín E Masip, Andrea V Bragas, Lía I Pietrasanta
The adhesion of cells to the extracellular matrix is a hierarchical, force-dependent, multistage process that evolves at several temporal scales. An understanding of this complex process requires a precise measurement of forces and its correlation with protein responses in living cells. We present a method to quantitatively assess live cell responses to a local and specific mechanical stimulus. Our approach combines atomic force microscopy with fluorescence imaging. Using this approach, we evaluated the recruitment of adhesion proteins such as vinculin, focal adhesion kinase, paxillin, and zyxin triggered by applying forces in the nN regime to live cells...
January 2017: Review of Scientific Instruments
https://www.readbyqxmd.com/read/28102310/coordinated-cell-motility-is-regulated-by-a-combination-of-lkb1-farnesylation-and-kinase-activity
#9
S Wilkinson, Y Hou, J T Zoine, J Saltz, C Zhang, Z Chen, L A D Cooper, A I Marcus
Cell motility requires the precise coordination of cell polarization, lamellipodia formation, adhesion, and force generation. LKB1 is a multi-functional serine/threonine kinase that associates with actin at the cellular leading edge of motile cells and suppresses FAK. We sought to understand how LKB1 coordinates these multiple events by systematically dissecting LKB1 protein domain function in combination with live cell imaging and computational approaches. We show that LKB1-actin colocalization is dependent upon LKB1 farnesylation leading to RhoA-ROCK-mediated stress fiber formation, but membrane dynamics is reliant on LKB1 kinase activity...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28005397/tns1-is-essential-for-myofibroblast-differentiation-and-extracellular-matrix-formation
#10
Ksenija Bernau, Elizabeth E Torr, Michael D Evans, Jason K Aoki, Caitlyn R Ngam, Nathan Sandbo
Myofibroblasts, the primary effector cells that mediate matrix remodeling during pulmonary fibrosis, rapidly assemble an extracellular fibronectin matrix1. Tensin1 (TNS1) is a key component of specialized cellular adhesions (fibrillar adhesions) that bind to extracellular fibronectin fibrils. We hypothesized that TNS1 may play a role in modulating myofibroblast-mediated matrix formation. We found that TNS1 expression is increased in fibroblastic foci from lungs with idiopathic pulmonary fibrosis. TGF-β profoundly upregulates TNS1 expression with kinetics that parallel the expression of the myofibroblast marker, ACTA2...
December 22, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27852899/local-arp2-3-dependent-actin-assembly-modulates-applied-traction-force-during-apcam-adhesion-site-maturation
#11
Kenneth B Buck, Andrew W Schaefer, Vincent T Schoonderwoert, Matthew S Creamer, Eric R Dufresne, Paul Forscher
Homophilic binding of immunoglobulin superfamily molecules such as the Aplysia cell adhesion molecule (apCAM) leads to actin filament assembly near nascent adhesion sites. Such actin assembly can generate significant localized forces that have not been characterized in the larger context of axon growth and guidance. We used apCAM-coated bead substrates applied to the surface of neuronal growth cones to characterize the development of forces evoked by varying stiffness of mechanical restraint. Unrestrained bead propulsion matched or exceeded rates of retrograde network flow and was dependent on Arp2/3 complex activity...
January 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27678055/persistence-of-fan-shaped-keratocytes-is-a-matrix-rigidity-dependent-mechanism-that-requires-%C3%AE-5%C3%AE-1-integrin-engagement
#12
Maryam Riaz, Marie Versaevel, Danahe Mohammed, Karine Glinel, Sylvain Gabriele
Despite the importance of matrix rigidity on cell functions, many aspects of the mechanosensing process in highly migratory cells remain elusive. Here, we studied the migration of highly motile keratocytes on culture substrates with similar biochemical properties and rigidities spanning the range between soft tissues (~kPa) and stiff culture substrates (~GPa). We show that morphology, polarization and persistence of motile keratocytes are regulated by the matrix stiffness over seven orders of magnitude, without changing the cell spreading area...
September 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27669437/the-focal-adhesion-associated-proteins-dock5-and-git2-comprise-a-rheostat-in-control-of-epithelial-invasion
#13
S R Frank, C P Köllmann, J F van Lidth de Jeude, J R Thiagarajah, L H Engelholm, M Frödin, S H Hansen
DOCK proteins are guanine nucleotide exchange factors for Rac and Cdc42 GTPases. DOCK1 is the founding member of the family and acts downstream of integrins via the canonical Crk-p130Cas complex to activate Rac GTPases in numerous contexts. In contrast, DOCK5, which possesses the greatest similarity to DOCK1, remains sparingly studied. Here we establish that DOCK5 has a non-redundant role in regulating motile and invasive capacities of epithelial cells. DOCK1 is constitutively associated with sites of integrin attachment termed focal adhesions (FAs)...
March 30, 2017: Oncogene
https://www.readbyqxmd.com/read/27637266/localized-translation-regulates-cell-adhesion-and-transendothelial-migration
#14
Jonathan Bergeman, Alexia Caillier, François Houle, Laurence M Gagné, Marc-Étienne Huot
By progressing through the epithelial to mesenchymal transition (EMT), cancer cells gain the ability to leave the primary tumor site and invade surrounding tissues. These metastatic cancers cells can further increase their plasticity by adopting an amoeboid-like morphology, by undergoing mesenchymal to amoeboid transition (MAT). We found that adhering cells producing spreading initiation centers (SIC), a transient structure localized above nascent adhesion complexes, share common biological and morphological characteristics associated with amoeboid cells...
September 16, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27354944/reconstruction-of-focal-femoral-head-cartilage-defects-with-a-chitin-based-scaffold
#15
Ahmed Al-Qarni, Matthew R Lewington, Ivan H Wong
It is well known that articular cartilage defects have little capability to heal. For grade III or IV cartilage defects, surgical intervention may be required for symptomatic patients. Microfracture is a commonly used surgical technique to address these injuries. However, microfracture has drawbacks, which include the risk of ossification of the newly formed tissue, as well as the imperfect and fragile nature of the fibrous cartilage. Given the challenges associated with microfracture, BST-CarGel (Piramal Healthcare, Laval, Quebec, Canada) has been developed to stabilize and support the nascent clot...
April 2016: Arthroscopy Techniques
https://www.readbyqxmd.com/read/27218451/cytoplasmic-notch-and-membrane-derived-%C3%AE-catenin-link-cell-fate-choice-to-epithelial-mesenchymal-transition-during-myogenesis
#16
Daniel Sieiro, Anne C Rios, Claire E Hirst, Christophe Marcelle
How cells in the embryo coordinate epithelial plasticity with cell fate decision in a fast changing cellular environment is largely unknown. In chick embryos, skeletal muscle formation is initiated by migrating Delta1-expressing neural crest cells that trigger NOTCH signaling and myogenesis in selected epithelial somite progenitor cells, which rapidly translocate into the nascent muscle to differentiate. Here, we uncovered at the heart of this response a signaling module encompassing NOTCH, GSK-3β, SNAI1 and β-catenin...
2016: ELife
https://www.readbyqxmd.com/read/27188911/claws-disorder-and-conformational-dynamics-of-the-c-terminal-region-of-human-desmoplakin
#17
Charles E McAnany, Cameron Mura
Multicellular organisms consist of cells that interact via elaborate adhesion complexes. Desmosomes are membrane-associated adhesion complexes that mechanically tether the cytoskeletal intermediate filaments (IFs) between two adjacent cells, creating a network of tough connections in tissues such as skin and heart. Desmoplakin (DP) is the key desmosomal protein that binds IFs, and the DP·IF association poses a quandary: desmoplakin must stably and tightly bind IFs to maintain the structural integrity of the desmosome...
August 25, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/27127172/integrin-signaling-via-fak-src-controls-cytokinetic-abscission-by-decelerating-plk1-degradation-and-subsequent-recruitment-of-cep55-at-the-midbody
#18
Siamak A Kamranvar, Deepesh Kumar Gupta, Ying Huang, Rajesh Kumar Gupta, Staffan Johansson
Adhesion to extracellular matrix is required for cell cycle progression through the G1 phase and for the completion of cytokinesis in normal adherent cells. Cancer cells acquire the ability to proliferate anchorage-independently, a characteristic feature of malignantly transformed cells. However, the molecular mechanisms underlying this escape of the normal control mechanisms remain unclear. The current study aimed to identify adhesion-induced reactions regulating the cytokinesis of non-transformed human fibroblasts...
May 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27053173/in-vivo-imaging-demonstrates-dendritic-spine-stabilization-by-syncam-1
#19
Nils Körber, Valentin Stein
Formation and stability of synapses are required for proper brain function. While it is well established that synaptic adhesion molecules are important regulators of synapse formation, their specific role during different phases of synapse development remains unclear. To investigate the function of the synaptic cell adhesion molecule SynCAM 1 in the formation, stability, and maintenance of spines we used 2-photon in vivo imaging to follow individual spines over a long period of time. In SynCAM 1 knockout mice the survival rate of existing spines was reduced and fewer filopodia-like structures were converted into stable spines...
April 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/26987342/substrate-engagement-of-integrins-%C3%AE-5%C3%AE-1-and-%C3%AE-v%C3%AE-3-is-necessary-but-not-sufficient-for-high-directional-persistence-in-migration-on-fibronectin
#20
Dimitris Missirlis, Tamás Haraszti, Catharina v C Scheele, Tina Wiegand, Carolina Diaz, Stefanie Neubauer, Florian Rechenmacher, Horst Kessler, Joachim P Spatz
The interplay between specific integrin-mediated matrix adhesion and directional persistence in cell migration is not well understood. Here, we characterized fibroblast adhesion and migration on the extracellular matrix glycoproteins fibronectin and vitronectin, focusing on the role of α5β1 and αvβ3 integrins. Fibroblasts manifested high directional persistence in migration on fibronectin-, but not vitronectin-coated substrates, in a ligand density-dependent manner. Fibronectin stimulated α5β1-dependent organization of the actin cytoskeleton into oriented, ventral stress fibers, and assembly of dynamic, polarized protrusions, characterized as regions free of stress fibers and rich in nascent adhesions at their edge...
March 18, 2016: Scientific Reports
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