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https://www.readbyqxmd.com/read/27913681/the-borg-family-of-cdc42-effector-proteins-cdc42ep1-5
#1
REVIEW
Aaron J Farrugia, Fernando Calvo
Despite being discovered more than 15 years ago, the Borg (binder of Rho GTPases) family of Cdc42 effector proteins (Cdc42EP1-5) remains largely uncharacterised and relatively little is known about their structure, regulation and role in development and disease. Recent studies are starting to unravel some of the key functional and mechanistic aspects of the Borg proteins, including their role in cytoskeletal remodelling and signalling. In addition, the participation of Borg proteins in important cellular processes such as cell shape, directed migration and differentiation is slowly emerging, directly linking Borgs with important physiological and pathological processes such as angiogenesis, neurotransmission and cancer-associated desmoplasia...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27913679/modelling-gtpase-dynamics-to-understand-rhoa-driven-cancer-cell-invasion
#2
REVIEW
Joseph H R Hetmanski, Jean-Marc Schwartz, Patrick T Caswell
Metastasis, initially driven by cells migrating and invading through the local environment, leads to most cancer-associated deaths. Cells can use a variety of modes to move in vitro, all of which depend on Rho GTPases at some level. While traditionally it was thought that Rac1 activity drives protrusive lamellipodia at the leading edge of a polarised cell while RhoA drives rear retraction, more recent work in 3D microenvironments has revealed a much more complicated picture of GTPase dynamics. In particular, RhoA activity can dominate the leading edge polymerisation of actin to form filopodial actin-spike protrusions that drive more invasive cell migration...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27911772/c-terminal-domain-ctd-phosphatase-links-rho-gtpase-signaling-to-pol-ii-ctd-phosphorylation-in-arabidopsis-and-yeast
#3
Bo Zhang, Guohua Yang, Yu Chen, Yihong Zhao, Peng Gao, Bo Liu, Haiyang Wang, Zhi-Liang Zheng
Rho GTPases, including the Rho, Cdc42, Rac, and ROP subfamilies, act as pivotal signaling switches in various growth and developmental processes. Compared with the well-defined role of cytoskeletal organization in Rho signaling, much less is known regarding transcriptional regulation. In a mutant screen for phenotypic enhancers of transgenic Arabidopsis plants expressing a constitutively active form of ROP2 (designated CA1-1), we identified RNA polymerase II (Pol II) C-terminal domain (CTD) phosphatase-like 1 (CPL1) as a transcriptional regulator of ROP2 signaling...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27910904/melanosome-transfer-to-keratinocyte-in-the-chicken-embryonic-skin-is-mediated-by-vesicle-release-associated-with-rho-regulated-membrane-blebbing
#4
Ryosuke Tadokoro, Hidetaka Murai, Ken-Ichiro Sakai, Takahiro Okui, Yasuhiro Yokota, Yoshiko Takahashi
During skin pigmentation in amniotes, melanin synthesized in the melanocyte is transferred to keratinocytes by a particle called the melanosome. Previous studies, mostly using dissociated cultured cells, have proposed several different models that explain how the melanosome transfer is achieved. Here, using a technique that labels the plasma membrane of melanocytes within a three-dimensional system that mimics natural tissues, we have visualized the plasma membrane of melanocytes with EGFP in chicken embryonic skin...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899881/transcriptomics-of-environmental-enrichment-reveals-a-role-for-retinoic-acid-signaling-in-addiction
#5
Yafang Zhang, Fanping Kong, Elizabeth J Crofton, Steven N Dragosljvich, Mala Sinha, Dingge Li, Xiuzhen Fan, Shyny Koshy, Jonathan D Hommel, Heidi M Spratt, Bruce A Luxon, Thomas A Green
There exists much variability in susceptibility/resilience to addiction in humans. The environmental enrichment paradigm is a rat model of resilience to addiction-like behavior, and understanding the molecular mechanisms underlying this protective phenotype may lead to novel targets for pharmacotherapeutics to treat cocaine addiction. We investigated the differential regulation of transcript levels using RNA sequencing of the rat nucleus accumbens after environmental enrichment/isolation and cocaine/saline self-administration...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27898263/genetic-alterations-affecting-gtpases-and-t-cell-receptor-signaling-in-peripheral-t-cell-lymphomas
#6
Rebecca L Boddicker, Gina L Razidlo, Andrew L Feldman
Peripheral T-cell lymphomas (PTCLs) are rare, heterogeneous tumors with poor response to standard therapy and few targeted treatments available. The identification of mutations in the T-cell receptor (TCR) signaling pathway that either directly or indirectly affect Ras- and Rho-family GTPases is an emerging theme across PTCL subtypes. This review summarizes the role of GTPases in TCR signaling and highlights the constellation of mutations in this pathway among PTCLs. In particular, focus is given to the functional impact of the mutations and opportunities for targeted therapy...
November 29, 2016: Small GTPases
https://www.readbyqxmd.com/read/27892645/endothelial-cell-derived-endothelin-1-is-involved-in-abnormal-scar-formation-by-dermal-fibroblasts-through-rhoa-rho-kinase-pathway
#7
Koichiro Kiya, Tateki Kubo, Kenichiro Kawai, Shinsuke Matsuzaki, Rieko Muramatsu, Daisuke Maeda, Toshihiro Fujiwara, Akimitsu Nishibayashi, Shigeyuki Kanazawa, Kenji Yano, Genki Amano, Taiichi Katayama, Ko Hosokawa
Hypertrophic scars and keloids are characterized by excessive dermal deposition of extracellular matrix due to fibroblast-to-myofibroblast differentiation. Endothelin-1 (ET-1) is primarily produced by vascular endothelial cells, and plays multiple roles in the wound-healing response and organ fibrogenesis. In this study, we investigated the pathophysiological significance of ET-1 and involvement of RhoA, a member of the Rho GTPases, in hypertrophic scar/keloid formation. We found that ET-1 expression on dermal microvascular endothelial cells (ECs) in hypertrophic scars and keloids was higher than that in normal skin and mature scars...
November 28, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27890731/mechanisms-of-cdc42-mediated-rat-msc-differentiation-on-micro-nano-textured-topography
#8
Guangwen Li, Yanyan Song, Mengqi Shi, Yuanhong Du, Wei Wang, Yumei Zhang
Micro/nano-textured titanium surface topography promotes osteoblast differentiation and the Wnt/β-catenin signaling pathway. However, the response of rat bone mesenchymal stem cells (MSCs) to micro/nano-textured topography, and the underlying mechanisms of its effects, are not well understood. We hypothesized that cell division cycle 42 protein (Cdc42), a key member of the Rho GTPases family, may regulate rat MSCs morphology and osteogenic differentiation by micro/nano-textured topography, and that crosstalk between Cdc42 and Wnt/ β -catenin is the underlying mechanism...
November 24, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27882344/slit2-robo2-signaling-pathway-inhibits-nonmuscle-myosin-iia-activity-and-destabilizes-kidney-podocyte-adhesion
#9
Xueping Fan, Hongying Yang, Sudhir Kumar, Kathleen E Tumelty, Anna Pisarek-Horowitz, Hila Milo Rasouly, Richa Sharma, Stefanie Chan, Edyta Tyminski, Michael Shamashkin, Mostafa Belghasem, Joel M Henderson, Anthony J Coyle, David J Salant, Stephen P Berasi, Weining Lu
The repulsive guidance cue SLIT2 and its receptor ROBO2 are required for kidney development and podocyte foot process structure, but the SLIT2/ROBO2 signaling mechanism regulating podocyte function is not known. Here we report that a potentially novel signaling pathway consisting of SLIT/ROBO Rho GTPase activating protein 1 (SRGAP1) and nonmuscle myosin IIA (NMIIA) regulates podocyte adhesion downstream of ROBO2. We found that the myosin II regulatory light chain (MRLC), a subunit of NMIIA, interacts directly with SRGAP1 and forms a complex with ROBO2/SRGAP1/NMIIA in the presence of SLIT2...
November 17, 2016: JCI Insight
https://www.readbyqxmd.com/read/27875099/the-rhob-small-gtpase-in-physiology-and-disease
#10
Francisco M Vega, Anne J Ridley
RhoB is a Rho family GTPase that is highly similar to RhoA and RhoC, yet has distinct functions in cells. Its unique C-terminal region is subject to specific post-translational modifications that confer different localization and functions to RhoB. Apart from the common role with RhoA and RhoC in actin organization and cell migration, RhoB is also implicated in a variety of other cellular processes including membrane trafficking, cell proliferation, DNA-repair and apoptosis. RhoB is not an essential gene in mice, but it is implicated in several physiological and pathological processes...
November 22, 2016: Small GTPases
https://www.readbyqxmd.com/read/27873143/regulation-of-rac1-gtpase-activity-by-quinine-through-g-protein-and-bitter-taste-receptor-t2r4
#11
Crystal Sidhu, Appalaraju Jaggupilli, Prashen Chelikani, Rajinder P Bhullar
Rac1 belongs to the Rho family of small GTPases and regulates actin cytoskeleton reorganization. T2R4 is a bitter taste receptor belonging to the G protein-coupled receptor family of proteins. In addition to mediating bitter taste perception from the tongue, T2R4s are found in extra-oral tissues, e.g., nasal epithelium, airways, brain, testis suggesting a much broader physiological function for these receptors. Anti-malarial drug and a bitter tasting compound, quinine, is a known agonist for T2R4, whereas BCML (Nα,Nα-Bis(carboxymethyl)-L-lysine) acts as an inverse agonist...
November 22, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27871818/oxidatively-generated-base-modifications-in-dna-not-only-carcinogenic-risk-factor-but-also-regulatory-mark
#12
Marco Seifermann, Bernd Epe
The generation of DNA modifications in cells is in most cases accidental and associated with detrimental consequences such as increased mutation rates and an elevated risk of malignant transformation. Accordingly, repair enzymes involved in the removal of the modifications have primarily a protective function. Among the well-established exceptions of this rule are 5-methylcytosine and uracil, which are generated in DNA enzymatically under controlled conditions and fulfill important regulatory functions in DNA as epigenetic marks and in antibody diversification, respectively...
November 18, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27864076/electric-field-as-a-potential-directional-cue-in-homing-of-bone-marrow-derived-mesenchymal-stem-cells-to-cutaneous-wounds
#13
Eliza Zimolag, Julia Borowczyk-Michalowska, Sylwia Kedracka-Krok, Bozena Skupien-Rabian, Elzbieta Karnas, Slawomir Lasota, Jolanta Sroka, Justyna Drukala, Zbigniew Madeja
Bone marrow-derived cells are thought to participate and enhance the healing process contributing to skin cells or releasing regulatory cytokines. Directional cell migration in a weak direct current electric field (DC-EF), known as electrotaxis, may be a way of cell recruitment to the wound site. Here we examined the influence of electric field on bone marrow adherent cells (BMACs) and its potential role as a factor attracting mesenchymal stem cells to cutaneous wounds. We observed that in an external EF, BMAC movement was accelerated and highly directed with distinction of two cell populations migrating toward opposite poles: mesenchymal stem cells migrated toward the cathode, whereas macrophages toward the anode...
November 15, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27861585/cdc-42-orients-cell-migration-during-epithelial-intercalation-in-the-caenorhabditis-elegans-epidermis
#14
Elise Walck-Shannon, Bethany Lucas, Ian Chin-Sang, David Reiner, Kraig Kumfer, Hunter Cochran, William Bothfeld, Jeff Hardin
Cell intercalation is a highly directed cell rearrangement that is essential for animal morphogenesis. As such, intercalation requires orchestration of cell polarity across the plane of the tissue. CDC-42 is a Rho family GTPase with key functions in cell polarity, yet its role during epithelial intercalation has not been established because its roles early in embryogenesis have historically made it difficult to study. To circumvent these early requirements, in this paper we use tissue-specific and conditional loss-of-function approaches to identify a role for CDC-42 during intercalation of the Caenorhabditis elegans dorsal embryonic epidermis...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27854239/kshv-entry-and-trafficking-in-target-cells-hijacking-of-cell-signal-pathways-actin-and-membrane-dynamics
#15
REVIEW
Binod Kumar, Bala Chandran
Kaposi's sarcoma associated herpesvirus (KSHV) is etiologically associated with human endothelial cell hyperplastic Kaposi's sarcoma and B-cell primary effusion lymphoma. KSHV infection of adherent endothelial and fibroblast cells are used as in vitro models for infection and KSHV enters these cells by host membrane bleb and actin mediated macropinocytosis or clathrin endocytosis pathways, respectively. Infection in endothelial and fibroblast cells is initiated by the interactions between multiple viral envelope glycoproteins and cell surface associated heparan sulfate (HS), integrins (α3β1, αVβ3 and αVβ5), and EphA2 receptor tyrosine kinase (EphA2R)...
November 14, 2016: Viruses
https://www.readbyqxmd.com/read/27852900/gradients-of-phosphatidylserine-contribute-to-plasma-membrane-charge-localization-and-cell-polarity-in-fission-yeast
#16
Armin Haupt, Nicolas Minc
Surface charges at the inner leaflet of the plasma membrane may contribute to regulate the surface recruitment of key signaling factors. Phosphatidylserine (PS) is an abundant charged lipid, which may regulate charge distribution in different cell types. In here, we characterize the subcellular distribution and function of PS in the rod-shaped, polarized fission yeast. We find that PS preferably accumulates at cell tips and defines a gradient of negative charges along the cell surface. This polarization depends on actin-mediated endocytosis and contributes to the subcellular partitioning of charged polarity-regulating Rho-GTPases like Rho1 or Cdc42 in a protein charge-dependent manner...
November 16, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27852828/emerging-biological-roles-of-cl-intracellular-channel-proteins
#17
REVIEW
Elisabetta Argenzio, Wouter H Moolenaar
Cl(-) intracellular channels (CLICs) are a family of six evolutionary conserved cytosolic proteins that exist in both soluble and membrane-associated forms; however, their functions have long been elusive. Soluble CLICs adopt a glutathione S-transferase (GST)-fold, can induce ion currents in artificial membranes and show oxidoreductase activity in vitro, but there is no convincing evidence of CLICs having such activities in vivo. Recent studies have revealed a role for CLIC proteins in Rho-regulated cortical actin dynamics as well as vesicular trafficking and integrin recycling, the latter of which are under the control of Rab GTPases...
November 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27852748/quantitative-gtpase-affinity-purification-identifies-rho-family-protein-interaction-partners
#18
Florian E Paul, Henrik Zauber, Laura von Berg, Oliver Rocks, Oliver Daumke, Matthias Selbach
Although Rho GTPases are essential molecular switches involved in many cellular processes, an unbiased experimental comparison of their interaction partners was not yet performed. Here, we develop quantitative GTPase affinity purification (qGAP) to systematically identify interaction partners of six Rho GTPases (Cdc42, Rac1, RhoA, RhoB, RhoC, RhoD) depending on their nucleotide loading state. The method works with cell line or tissue-derived protein lysates in combination with SILAC-based or label free quantification, respectively...
November 16, 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27849309/activation-of-rac1-and-rhoa-preserve-corneal-endothelial-barrier-function
#19
María C Ortega, Diana Santander-García, Beatriz Marcos-Ramiro, Susana Barroso, Susan Cox, Ignacio Jiménez-Alfaro, Jaime Millán
Purpose: The corneal endothelium is responsible for the correct hydration of the corneal stroma. Corneal endothelial cells have a low proliferative capacity, so preserving their barrier function under suboptimal conditions that cause osmotic imbalance, such as those arising from corneal pathologies, age, cryopreservation, and transplantation, is essential for maintaining corneal transparency. We have investigated the signaling induced by hyperosmotic shock that reversibly disrupts corneal endothelial barriers in human endothelial cells and in murine corneas...
November 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27837107/rac2-functions-in-both-neutrophils-and-macrophages-to-mediate-motility-and-host-defense-in-larval-zebrafish
#20
Emily E Rosowski, Qing Deng, Nancy P Keller, Anna Huttenlocher
Leukocyte motility is required for host defense responses. Rac-family Rho GTPases are implicated in leukocyte function; however, the distinct roles of different Rac isoforms in host defense in vivo have remained unclear. In this study, we generated Rac2-deficient zebrafish using transcription activator-like effector nucleases to directly compare the role of Rac2 in vivo in neutrophils and macrophages in motility and the response to infection. This zebrafish larval model is highly amenable to live imaging of leukocyte behavior, and we report that in rac2(-/-) larvae both neutrophils and macrophages are defective in basic motility, leading to impaired responses to localized wounds or infections...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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