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https://www.readbyqxmd.com/read/29780159/modulation-of-store-operated-calcium-entry-and-nascent-adhesion-by-p21-activated-kinase-1
#1
In-Sook Jeon, Hye-Ryun Kim, Eun-Young Shin, Eung-Gook Kim, Heon-Seok Han, Jin-Tae Hong, Hak-Kyo Lee, Ki-Duk Song, Joong-Kook Choi
Calcium mobilization is necessary for cell movement during embryonic development, lymphocyte synapse formation, wound healing, and cancer cell metastasis. Depletion of calcium in the lumen of the endoplasmic reticulum using inositol triphosphate (IP3) or thapsigargin (TG) is known to induce oligomerization and cytoskeleton-mediated translocation of stromal interaction molecule 1 (STIM1) to the plasma membrane, where it interacts with the calcium release-activated calcium channel Orai1 to mediate calcium influx; this process is referred to as store-operated calcium entry (SOCE)...
May 21, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29748378/myosin-1c-promotes-e-cadherin-tension-and-force-dependent-recruitment-of-%C3%AE-actinin-4-to-the-epithelial-cell-junction
#2
Nivetha Kannan, Vivian W Tang
Actomyosin II contractility in epithelial cell plays an essential role in tension-dependent adhesion strengthening. One key unsettling question is how cellular contraction transmits force to the nascent cell-cell adhesion when there is no stable attachment between the nascent adhesion complex and actin filament. Here, we show that myosin-1c is localized to the lateral membrane of polarized epithelial cells and facilitates the coupling between actin and cell-cell adhesion. Knockdown of myosin-1c compromised the integrity of the lateral membrane, reduced the generation of tension at E-cadherin, decreased the strength of cell-cell cohesion in an epithelial cell monolayer, and prevented force-dependent recruitment of junctional α-actinin-4...
May 10, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29740649/traction-cytometry-regularization-in-the-fourier-approach-and-comparisons-with-finite-element-method
#3
Ankur H Kulkarni, Prasenjit Ghosh, Ashwin Seetharaman, Paturu Kondaiah, Namrata Gundiah
Traction forces exerted by adherent cells are quantified using displacements of embedded markers on polyacrylamide substrates due to cell contractility. Fourier Transform Traction Cytometry (FTTC) is widely used to calculate tractions but has inherent limitations due to errors in the displacement fields; these are mitigated through a regularization parameter (γ) in the Reg-FTTC method. An alternate finite element (FE) approach computes tractions on a domain using known boundary conditions. Robust verification and recovery studies are lacking but essential in assessing the accuracy and noise sensitivity of the traction solutions from the different methods...
May 9, 2018: Soft Matter
https://www.readbyqxmd.com/read/29731254/filopodia-conduct-target-selection-in-cortical-neurons-using-differences-in-signal-kinetics-of-a-single-kinase
#4
Yu-Ting Mao, Julia X Zhu, Kenji Hanamura, Giuliano Iurilli, Sandeep Robert Datta, Matthew B Dalva
Dendritic filopodia select synaptic partner axons by interviewing the cell surface of potential targets, but how filopodia decipher the complex pattern of adhesive and repulsive molecular cues to find appropriate contacts is unknown. Here, we demonstrate in cortical neurons that a single cue is sufficient for dendritic filopodia to reject or select specific axonal contacts for elaboration as synaptic sites. Super-resolution and live-cell imaging reveals that EphB2 is located in the tips of filopodia and at nascent synaptic sites...
April 30, 2018: Neuron
https://www.readbyqxmd.com/read/29570686/design-synthesis-and-biological-evaluation-of-axitinib-derivatives
#5
Na Wei, Jianqing Liang, Shengming Peng, Qiang Sun, Qiuyun Dai, Mingxin Dong
Axitinib is an approved kinase inhibitor for the therapy of advanced metastatic renal cell carcinoma (RCC). It prevents angiogenesis, cellular adhesion, and induces apoptosis of cancer cells. Here, nine axitinib derivatives were designed by replacing the C=C moiety with the N=N group, and the substituted benzene or pyrrole analogs were considered to replace the pyridine ring. Biological activity results showed that most of nascent derivatives exhibited favorable VEGFR-2 kinase inhibitory activities, and TM6 , 7 , 9 , and 11 behaved more potent anti-proliferative activities than axitinib...
March 23, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29549720/enhancing-clot-properties-through-fibrin-specific-self-cross-linked-peg-side-chain-microgels
#6
Nicole Welsch, Ashley C Brown, Thomas H Barker, L Andrew Lyon
Excessive bleeding and resulting complications are a major cause of death in both trauma and surgical settings. Recently, there have been a number of investigations into the design of synthetic hemostatic agents with platelet-mimicking activity to effectively treat patients suffering from severe hemorrhage. We developed platelet-like particles from microgels composed of polymers carrying polyethylene glycol (PEG) side-chains and fibrin-targeting single domain variable fragment antibodies (PEG-PLPs). Comparable to natural platelets, PEG-PLPs were found to enhance the fibrin network formation in vitro through strong adhesion to the emerging fibrin clot and physical, non-covalent cross-linking of nascent fibrin fibers...
June 1, 2018: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29504935/neurexin-and-neuroligin-based-adhesion-complexes-drive-axonal-arborisation-growth-independent-of-synaptic-activity
#7
William D Constance, Amrita Mukherjee, Yvette E Fisher, Sinziana Pop, Eric Blanc, Yusuke Toyama, Darren W Williams
Building arborisations of the right size and shape is fundamental for neural network function. Live imaging in vertebrate brains strongly suggests that nascent synapses are critical for branch growth during development. The molecular mechanisms underlying this are largely unknown. Here we present a novel system in Drosophila for studying the development of complex arborisations live, in vivo during metamorphosis. In growing arborisations we see branch dynamics and localisations of presynaptic proteins very similar to the 'synaptotropic growth' described in fish/frogs...
March 5, 2018: ELife
https://www.readbyqxmd.com/read/29487208/lamellipodium-is-a-myosin-independent-mechanosensor
#8
Patrick W Oakes, Tamara C Bidone, Yvonne Beckham, Austin V Skeeters, Guillermina R Ramirez-San Juan, Stephen P Winter, Gregory A Voth, Margaret L Gardel
The ability of adherent cells to sense changes in the mechanical properties of their extracellular environments is critical to numerous aspects of their physiology. It has been well documented that cell attachment and spreading are sensitive to substrate stiffness. Here, we demonstrate that this behavior is actually biphasic, with a transition that occurs around a Young's modulus of ∼7 kPa. Furthermore, we demonstrate that, contrary to established assumptions, this property is independent of myosin II activity...
March 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29486368/bone-toughness-at-the-molecular-scale-a-model-for-fracture-toughness-using-crosslinked-osteopontin-on-synthetic-and-biogenic-mineral-substrates
#9
S Cavelier, A K Dastjerdi, M D McKee, F Barthelat
The most prominent structural components in bone are collagen and mineral. However, bone additionally contains a substantial amount of noncollagenous proteins (most notably of the SIBLING protein family), some of which may act as cohesive/adhesive "binders" for the composite hybrid collagen/mineral scaffolding, whether in the bulk phase of bone, or at its interfaces. One such noncollagenous protein - osteopontin (OPN) - appears to be critical to the deformability and fracture toughness of bone. In the present study, we used a reconstructed synthetic mineral-OPN-mineral interface, and a biogenic (natural tooth dentin) mineral/collagen-OPN-mineral/collagen interface, to measure the fracture toughness of OPN on mineralized substrates...
May 2018: Bone
https://www.readbyqxmd.com/read/29401618/regulation-of-il-1-signaling-through-control-of-focal-adhesion-assembly
#10
Qin Wang, Julie Delcorde, Tracy Tang, Gregory P Downey, Christopher A McCulloch
IL-1 signaling is adhesion-restricted in many cell types, but the mechanism that drives it is not defined. We screened for proteins recruited to nascent adhesions in IL-1-treated human fibroblasts with tandem mass tag-mass spectrometry. We used fibronectin bead preparations to enrich 10 actin-associated proteins. There was a 1.2 times log 2-fold enrichment of actin capping protein (ACP) at 30 min after IL-1 stimulation. Knockdown (KD) of ACP by siRNA reduced IL-1-induced ERK activation(by 56%, matrix metalloproteinase-3 (MMP-3) expression by 48%, and MMP-9 expression by 62% (in all reductions, P < 0...
January 22, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29379062/spatiotemporal-patterning-of-epcam-is-important-for-murine-embryonic-endo-and-mesodermal-differentiation
#11
Sannia Sarrach, Yuanchi Huang, Sebastian Niedermeyer, Matthias Hachmeister, Laura Fischer, Sebastian Gille, Min Pan, Brigitte Mack, Gisela Kranz, Darko Libl, Juliane Merl-Pham, Stefanie M Hauck, Elisa Paoluzzi Tomada, Matthias Kieslinger, Irmela Jeremias, Antonio Scialdone, Olivier Gires
Epithelial cell adhesion molecule EpCAM is expressed in pluripotent embryonic stem cells (ESC) in vitro, but is repressed in differentiated cells, except epithelia and carcinomas. Molecular functions of EpCAM, possibly imposing such repression, were primarily studied in malignant cells and might not apply to non-pathologic differentiation. Here, we comprehensively describe timing and rationale for EpCAM regulation in early murine gastrulation and ESC differentiation using single cell RNA-sequencing datasets, in vivo and in vitro models including CRISPR-Cas9-engineered ESC-mutants...
January 29, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29356434/5-chloro-2-4-dihydroxypyridine-cdhp-prevents-lung-metastasis-of-basal-like-breast-cancer-cells-by-reducing-nascent-adhesion-formation
#12
Junji Itou, Hiroshi Tsukihara, Mamoru Nukatsuka, Masakazu Toi, Teiji Takechi
A drug for metastasis prevention is necessary. The orally administered anticancer drug S-1 contributes to cancer therapy. In a mouse xenograft model of metastatic breast cancer from our previous study, the administration of S-1 inhibited lung metastasis. However, the mechanism of inhibition remains elusive. S-1 contains 5-chloro-2,4-dihydroxypyridine (CDHP), which does not have the antigrowth activity, but prevents the degradation of 5-fluorouracil, an anticancer reagent. In this study, we found that CDHP treatment shrinks cell morphology in metastatic basal-like breast cancer cell lines...
February 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29330179/influence-of-type-i-fimbriae-and-fluid-shear-stress-on-bacterial-behavior-and-multicellular-architecture-of-early-escherichia-coli-biofilms-at-single-cell-resolution
#13
Liyun Wang, Robert Keatch, Qi Zhao, John A Wright, Clare E Bryant, Anna L Redmann, Eugene M Terentjev
Biofilm formation on abiotic surfaces in food and medical industry can cause severe contamination and infection, yet how biological and physical factors determine cellular architecture of early biofilms and bacterial behavior of the constituent cells remains largely unknown. In this study we examine the specific role of type-I fimbriae in nascent stages of biofilm formation and the response of micro-colonies to environmental flow shear at single-cell resolution. The results show that type-I fimbriae are not required for reversible adhesion from plankton, but critical for irreversible adhesion of Escherichia coli ( E...
January 12, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29133936/the-rho-gtpase-signalling-pathway-in-urothelial-carcinoma
#14
REVIEW
Solomon L Woldu, Ryan C Hutchinson, Laura-Maria Krabbe, Oner Sanli, Vitaly Margulis
Urothelial carcinoma remains a clinical challenge: non-muscle-invasive disease has a high rate of recurrence and risk of progression, and outcomes for patients with advanced disease are poor, owing to a lack of effective systemic therapies. The Rho GTPase family of enzymes was first identified >30 years ago and contains >20 members, which are divided into eight subfamilies: Cdc42, Rac, Rho, RhoUV, RhoBTB, RhoDF, RhoH, and Rnd. Rho GTPases are molecular on-off switches, which are increasingly being understood to have a critical role in a number of cellular processes, including cell migration, cell polarity, cell adhesion, cell cycle progression, and regulation of the cytoskeleton...
February 2018: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29069646/the-intracranial-aneurysm-gene-thsd1-connects-endosome-dynamics-to-nascent-focal-adhesion-assembly
#15
Yan-Ning Rui, Zhen Xu, Xiaoqian Fang, Miriam R Menezes, Julien Balzeau, Airu Niu, John P Hagan, Dong H Kim
BACKGROUND/AIMS: We recently discovered that harmful variants in THSD1 (Thrombospondin type-1 domain-containing protein 1) likely cause intracranial aneurysm and subarachnoid hemorrhage in a subset of both familial and sporadic patients with supporting evidence from two vertebrate models. The current study seeks to elucidate how THSD1 and patient-identified variants function molecularly in focal adhesions. METHODS: Co-immunostaining and co-immunoprecipitation were performed to define THSD1 subcellular localization and interacting partners...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29057977/myosin-x-is-recruited-to-nascent-focal-adhesions-at-the-leading-edge-and-induces-multi-cycle-filopodial-elongation
#16
Kangmin He, Tsuyoshi Sakai, Yoshikazu Tsukasaki, Tomonobu M Watanabe, Mitsuo Ikebe
Filopodia protrude from the leading edge of cells and play important roles in cell motility. Here we report the mechanism of myosin X (encoded by Myo10)-induced multi-cycle filopodia extension. We found that actin, Arp2/3, vinculin and integrin-β first accumulated at the cell's leading edge. Myosin X was then gathered at these sites, gradually clustered by lateral movement, and subsequently initiated filopodia formation. During filopodia extension, we found the translocation of Arp2/3 and integrin-β along filopodia...
October 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28917158/quantitative-trait-locus-mapping-in-mice-identifies-phospholipase-pla2g12a-as-novel-atherosclerosis-modifier
#17
Alexandros Nicolaou, Bernd H Northoff, Kristina Sass, Jana Ernst, Alexander Kohlmaier, Knut Krohn, Christian Wolfrum, Daniel Teupser, Lesca M Holdt
BACKGROUND AND AIMS: In a previous work, a female-specific atherosclerosis risk locus on chromosome (Chr) 3 was identified in an intercross of atherosclerosis-resistant FVB and atherosclerosis-susceptible C57BL/6 (B6) mice on the LDL-receptor deficient (Ldlr(-/-)) background. It was the aim of the current study to identify causative genes at this locus. METHODS: We established a congenic mouse model, where FVB.Chr3(B6/B6) mice carried an 80 Mb interval of distal Chr3 on an otherwise FVB...
September 4, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28912124/kindlin-2-recruits-paxillin-and-arp2-3-to-promote-membrane-protrusions-during-initial-cell-spreading
#18
Ralph T Böttcher, Maik Veelders, Pascaline Rombaut, Jan Faix, Marina Theodosiou, Theresa E Stradal, Klemens Rottner, Roy Zent, Franz Herzog, Reinhard Fässler
Cell spreading requires the coupling of actin-driven membrane protrusion and integrin-mediated adhesion to the extracellular matrix. The integrin-activating adaptor protein kindlin-2 plays a central role for cell adhesion and membrane protrusion by directly binding and recruiting paxillin to nascent adhesions. Here, we report that kindlin-2 has a dual role during initial cell spreading: it binds paxillin via the pleckstrin homology and F0 domains to activate Rac1, and it directly associates with the Arp2/3 complex to induce Rac1-mediated membrane protrusions...
November 6, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28877491/%C3%AE-1-integrin-mediated-adhesion-is-lipid-bilayer-dependent
#19
Seoyoung Son, George J Moroney, Peter J Butler
Integrin-mediated adhesion is a central feature of cellular adhesion, locomotion, and endothelial cell mechanobiology. Although integrins are known to be transmembrane proteins, little is known about the role of membrane biophysics and dynamics in integrin adhesion. We treated human aortic endothelial cells with exogenous amphiphiles, shown previously in model membranes, and computationally, to affect bilayer thickness and lipid phase separation, and subsequently measured single-integrin-molecule adhesion kinetics using an optical trap, and diffusion using fluorescence correlation spectroscopy...
September 5, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28747994/lignin-valorization-lignin-nanoparticles-as-high-value-bio-additive-for-multifunctional-nanocomposites
#20
Dong Tian, Jinguang Hu, Jie Bao, Richard P Chandra, Jack N Saddler, Canhui Lu
BACKGROUND: Although conversion of low value but high-volume lignin by-product to its usable form is one of the determinant factors for building an economically feasible integrated lignocellulose biorefinery, it has been challenged by its structural complexity and inhomogeneity. We and others have shown that uniform lignin nanoparticles can be produced from a wide range of technical lignins, despite the varied lignocellulosic biomass and the pretreatment methods/conditions applied. This value-added nanostructure lignin enriched with multifunctional groups can be a promising versatile material platform for various downstream utilizations especially in the emerging nanocomposite fields...
2017: Biotechnology for Biofuels
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