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Rho GTPases

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https://www.readbyqxmd.com/read/28548879/ras-and-rho-gtpase-regulation-of-pol-ii-transcription-a-shortcut-model-revisited
#1
Zhi-Liang Zheng
Transcriptional control is critical in relaying signals mediated by Ras and Rho family small GTPases to effect gene expression. In the classical model, signaling components such as MAP kinase target sequence-specific transcription factors, which in turn recruit RNA polymerase (Pol) II holoenzyme to the promoter and activate transcription. Findings in recent years have led to the proposal of a shortcut model in which the mediator components of the Pol II holoenzyme are regulated by signaling pathways. A very recent finding shows that an evolutionarily conserved Rho GTPase signaling pathway can directly modulate the Pol II C-terminal domain (CTD) phosphorylation by inhibiting the CTD phosphatase in yeast and Arabidopsis...
May 26, 2017: Transcription
https://www.readbyqxmd.com/read/28548571/correlation-of-cdc42-activity-with-cell-proliferation-and-palmitate-mediated-cell-death-in-human-umbilical-cord-wharton-s-jelly-derived-mesenchymal-stromal-cells
#2
Jun Lu, Qinghua Wang, Lianghu Huang, Huiyue Dong, Lingjing Lin, Jianming Tan
RHO GTPases regulate cell migration, cell-cycle progression, and cell survival in response to extracellular stimuli. However, the regulatory effects of RHO GTPases in mesenchymal stromal cells (MSCs) are unclear. Herein, we show that CDC42 acts as an essential factor in regulating cell proliferation and also takes part in lipotoxic effects of palmitate in human umbilical cord Wharton's jelly derived MSCs (hWJ-MSCs). Cultured human bone marrow (hBM-MSCs), adipose tissue (hAD-MSCs), and umbilical cord Wharton's jelly (hWJ-MSCs) derived cells had varying pro-inflammatory cytokine secretion levels and cell death rates when treated by palmitate...
May 26, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28541439/the-evolutionary-landscape-of-dbl-like-rhogef-families-adapting-eukaryotic-cells-to-environmental-signals
#3
Philippe Fort, Anne Blangy
The dynamics of cell morphology in eukaryotes is largely controlled by small GTPases of the Rho family. Rho GTPases are activated by Guanine nucleotide Exchange Factors (RhoGEFs), of which Diffuse B-cell Lymphoma (Dbl)-like members form the largest family. Here we surveyed Dbl-like sequences from 175 eukaryotic genomes and illuminate how the Dbl family evolved in all eukaryotic supergroups. By combining probabilistic phylogenetic approaches and functional domain analysis, we show that the human Dbl-like family is made of 71 members, structured into 20 subfamilies...
May 25, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28538170/yap-regulates-actin-dynamics-through-arhgap29-and-promotes-metastasis
#4
Yiting Qiao, Jianxiang Chen, Ying Bena Lim, Megan Louise Finch-Edmondson, Veerabrahma Pratap Seshachalam, Lei Qin, Tingting Jiang, Boon Chuan Low, Himanshu Singh, Chwee Teck Lim, Marius Sudol
Yes-associated protein (YAP) is regulated by mechanical cues via the interaction of the Hippo pathway with cytoskeleton. Previous studies showed that YAP plays a role in regulating the actomyosin network by suppressing Rho GTPase in medaka fish. Here, we identify Rho GTPase activating protein 29 (ARHGAP29) as a transcriptional target of YAP in a human gastric cancer cell line. YAP promotes the expression of ARHGAP29 to suppress the RhoA-LIMK-cofilin pathway, destabilizing F-actin. The overexpression of YAP causes cytoskeletal rearrangement by altering the dynamics of F-actin/G-actin turnover, thus promoting migration...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28528353/adrenomedullin-ameliorates-podocyte-injury-induced-by-puromycin-aminonucleoside-in-vitro-and-in-vivo-through-modulation-of-rho-gtpases
#5
Nan Dong, Lixia Meng, Ruqun Xue, Meng Yu, Zhonghua Zhao, Xueguang Liu
PURPOSE: Podocyte injury is a key event in proteinuric kidney disease and eventually glomerular scarring. While adrenomedullin (AM), a potent vasodilatory peptide, has been reported to confer renoprotection in several experimental models of kidney diseases, its effect on injured podocytes and the related mechanism is still largely unknown. METHODS: Employing Western blotting analysis, immunoprecipitation and immunofluorescence, we investigated the effects of AM on the expressions of podocyte cytoskeletal proteins and Rho-family small GTPases (Rho GTPases) in puromycin aminonucleoside (PAN)-induced podocyte injury, both in cultured podocytes and in PAN nephrosis rats...
May 20, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28527113/mutant-p53-promotes-cell-spreading-and-migration-via-arhgap44
#6
Jinjin Xu, Jian Jiao, Wei Xu, Lei Ji, Dongjie Jiang, Shaofang Xie, Syeda Kubra, Xiaotao Li, Junjiang Fu, Jianru Xiao, Bianhong Zhang
The tumor suppressor p53 protein is either lost or mutated in about half of all human cancers. Loss of p53 function is well known to influence cell spreading, migration and invasion. While expression of mutant p53 is not equivalent to p53 loss, mutant p53 can acquire new functions to drive cell spreading and migration via different mechanisms. In our study, we found that mutant p53 significantly increased cell spreading and migration when comparing with p53-null cells. RNA-Seq analysis suggested that Rho GTPase activating protein 44 (ARHGAP44) is a new target of mutant p53, which suppressed ARHGAP44 transcription...
May 16, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28524846/concerted-regulation-of-retinal-pigment-epithelium-basement-membrane-and-barrier-function-by-angiocrine-factors
#7
Ignacio Benedicto, Guillermo L Lehmann, Michael Ginsberg, Daniel J Nolan, Rohan Bareja, Olivier Elemento, Zelda Salfati, Nazia M Alam, Glen T Prusky, Pierre Llanos, Sina Y Rabbany, Arvydas Maminishkis, Sheldon S Miller, Shahin Rafii, Enrique Rodriguez-Boulan
The outer blood-retina barrier is established through the coordinated terminal maturation of the retinal pigment epithelium (RPE), fenestrated choroid endothelial cells (ECs) and Bruch's membrane, a highly organized basement membrane that lies between both cell types. Here we study the contribution of choroid ECs to this process by comparing their gene expression profile before (P5) and after (P30) the critical postnatal period when mice acquire mature visual function. Transcriptome analyses show that expression of extracellular matrix-related genes changes dramatically over this period...
May 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28524754/arf-gtpase-interplay-with-rho-gtpases-in-regulation-of-the-actin-cytoskeleton
#8
Vikash Singh, Anthony C Davidson, Peter J Hume, Daniel Humphreys, Vassilis Koronakis
The Arf and Rho subfamilies of small GTPases are nucleotide-dependent molecular switches that act as master regulators of vesicular trafficking and the actin cytoskeleton organization. Small GTPases control cell processes with high fidelity by acting through distinct repertoires of binding partners called effectors. While we understand a great deal about how these GTPases act individually, relatively little is known about how they cooperate, especially in the control of effectors. This review highlights how Arf GTPases collaborate with Rac1 to regulate actin cytoskeleton dynamics at the membrane via recruiting and activating the Wave Regulatory Complex (WRC), a Rho effector that underpins lamellipodia formation and macropinocytosis...
May 19, 2017: Small GTPases
https://www.readbyqxmd.com/read/28521592/molecular-perturbation-strategies-to-examine-spatiotemporal-features-of-rho-gef-and-rho-gtpase-activity-in-living-cells
#9
Joachim Goedhart, Jakobus van Unen
Much of our current knowledge of Rho GTPase networks and the regulation by Rho guanine exchange factors (Rho GEFs) and Rho GTPase activating proteins (Rho GAPs) is based on population-based techniques. Over the last decades, technologies that enable single cell analysis with high spatial and temporal resolution have revealed that Rho GTPase activity in cells is regulated on second timescales and at submicrometer length scales. Therefore, perturbation methods with matching spatial and temporal resolution are crucial to further our understanding of Rho GTPase signaling...
May 19, 2017: Small GTPases
https://www.readbyqxmd.com/read/28513223/activation-of-thromboxane-a2-receptors-mediates-endothelial-dysfunction-in-diabetic-mice
#10
Xiaona Xie, Wanchun Sun, Jun Wang, Xiaoou Li, Xiaofeng Liu, Ning Liu
BACKGROUND: Diabetes is one of high-risk factors for cardiovascular disease. Improvement of endothelial dysfunction in diabetes reduces vascular complications. However, the underlying mechanism needs to be uncovered. This study was conducted to elucidate whether and how thromboxane A2 receptor (TPr) activation contributes to endothelial dysfunction in diabetes. METHODS AND RESULTS: Exposure of human umbilical vein endothelial cells (HUVECs) to either TPr agonists, two structurally related thromboxane A2 (TxA2) mimetics, significantly reduced phosphorylations of endothelial nitric oxide synthase (eNOS) at Ser(1177) and Akt at Ser(473)...
May 17, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28512143/diverse-roles-of-guanine-nucleotide-exchange-factors-in-regulating-collective-cell-migration
#11
Assaf Zaritsky, Yun-Yu Tseng, M Angeles Rabadán, Shefali Krishna, Michael Overholtzer, Gaudenz Danuser, Alan Hall
Efficient collective migration depends on a balance between contractility and cytoskeletal rearrangements, adhesion, and mechanical cell-cell communication, all controlled by GTPases of the RHO family. By comprehensive screening of guanine nucleotide exchange factors (GEFs) in human bronchial epithelial cell monolayers, we identified GEFs that are required for collective migration at large, such as SOS1 and β-PIX, and RHOA GEFs that are implicated in intercellular communication. Down-regulation of the latter GEFs differentially enhanced front-to-back propagation of guidance cues through the monolayer and was mirrored by down-regulation of RHOA expression and myosin II activity...
May 16, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28510328/genetic-variants-in-the-genes-encoding-rho-gtpases-and-related-regulators-predict-cutaneous-melanoma-specific-survival
#12
Shun Liu, Yanru Wang, William Xue, Hongliang Liu, Yinghui Xu, Qiong Shi, Wenting Wu, Dakai Zhu, Christopher I Amos, Shenying Fang, Jeffrey E Lee, Terry Hyslop, Yi Li, Jiali Han, Qingyi Wei
Rho GTPases control cell division, motility, adhesion, vesicular trafficking and phagocytosis, which may affect progression and/or prognosis of cancers. Here, we investigated associations between genetic variants of Rho GTPases-related genes and cutaneous melanoma-specific survival (CMSS) by re-analyzing a published melanoma genome-wide association study (GWAS) and validating the results in another melanoma GWAS. In the single-locus analysis of 36,018 SNPs in 129 Rho-related genes, 427 SNPs were significantly associated with CMSS (P<0...
May 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28508825/abcs-of-rhogtpases-indicating-potential-role-as-oncotargets
#13
REVIEW
Indira Bora, Neeta Shrivastava
RhoGTPases also known as molecular switches represent a family of GTP-binding proteins. They shuttle between "On" and "Off" states. In the "On" state, they activate plethora of molecules. These proteins perform a wide variety of functions involving cytoskeletal modeling, cell motility, migration, and mitosis. Members of this family are referred as master regulators of many cellular activities. Due to wide variety of portfolios attributed to RhoGTPases, their misbehavior leads to initiation and also progression of metastatic cancers...
January 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28505515/rhob-induces-the-production-of-proinflammatory-cytokines-in-tlr-triggered-macrophages
#14
Shuyuan Liu, Lisong Huang, Zhusen Lin, Yuanqin Hu, Ruifeng Chen, Liqiu Wang, Yi Shan
Toll-like receptors (TLRs) are the primary sensors detecting conserved molecular patterns on microorganisms, thus acting as important components of innate immunity against invading pathogens. Many positive and negative regulators of TLR-triggered signaling have been identified. The Rho GTPase RhoB plays a key role in cell migration, division and polarity; however, the function and regulatory mechanisms of RhoB in TLR ligand-triggered innate immune responses remain to be investigated. Here, we report that the expression of RhoB is induced by TLR agonists (lipopolysaccharide (LPS), CpG, poly(I:C)) in macrophages...
May 12, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28502648/control-of-astrocyte-morphology-by-rho-gtpases
#15
REVIEW
Andre Zeug, Franziska E Müller, Stefanie Anders, Michel K Herde, Daniel Minge, Evgeni Ponimaskin, Christian Henneberger
Astrocytes modulate and support neuronal and synapse function via numerous mechanisms that often rely on diffusion of signalling molecules, ions or metabolites through extracellular space. As a consequence, the spatial arrangement and the distance between astrocyte processes and neuronal structures is of functional importance. Likewise, changes of astrocyte structure will affect the ability of astrocytes to interact with neurons. In contrast to neurons, where rapid morphology changes are critically involved in many aspects of physiological brain function, a role of astrocyte restructuring in brain physiology is only beginning to emerge...
May 11, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28500512/molecular-adaptations-to-social-defeat-stress-and-induced-depression-in-mice
#16
Natalya Bondar, Leonid Bryzgalov, Nikita Ershov, Fedor Gusev, Vasiliy Reshetnikov, Damira Avgustinovich, Mikhail Tenditnik, Evgeny Rogaev, Tatiana Merkulova
Chronic stress is a risk factor for major depression. Social defeat stress is a well-validated murine model of depression. However, little is known about the gene activity dynamics during the development of a depression-like state. We analyzed the effects of social defeat stress of varying duration (10 and 30 days) on the behavioral patterns and prefrontal-cortex transcriptome of C57BL/6 mice. The 10-day exposure to social defeat stress resulted in a high level of social avoidance with no signs of depression-associated behavior...
May 12, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28499439/the-role-of-tgf-%C3%AE-and-its-crosstalk-with-rac1-rac1b-signaling-in-breast-and-pancreas-carcinoma
#17
REVIEW
Catharina Melzer, Ralf Hass, Juliane von der Ohe, Hendrik Lehnert, Hendrik Ungefroren
This article focusses on the role of TGF-β and its signaling crosstalk with the RHO family GTPases RAC1 and RAC1b in the progression of breast and pancreatic carcinoma. The aggressive nature of these tumor types is mainly due to metastatic dissemination. Metastasis is facilitated by desmoplasia, a peculiar tumor microenvironment and the ability of the tumor cells to undergo epithelial-mesenchymal transition (EMT) and to adopt a motile and invasive phenotype. These processes are controlled entirely or in part by TGF-β and the small RHO GTPase RAC1 with both proteins acting as tumor promoters in late-stage cancers...
May 12, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28498728/a-family-affair-a-ral-exocyst-centered-network-links-ras-rac-rho-signaling-to-control-cell-migration
#18
Giulia Zago, Marco Biondini, Jacques Camonis, Maria Carla Parrini
Cell migration is central to many developmental, physiologic and pathological processes, including cancer progression. The Ral GTPases (RalA and RalB) which act down-stream the Ras oncogenes, are key players in the coordination between membrane trafficking and actin polymerization. A major direct effector of Ral, the exocyst complex, works in polarized exocytosis and is at the center of multiple protein-protein interactions that support cell migration by promoting protrusion formation, front-rear polarization, and extra-cellular matrix degradation...
May 12, 2017: Small GTPases
https://www.readbyqxmd.com/read/28493540/corrigendum-a-gal4-inducible-transgenic-tool-kit-for-the-in-vivo-modulation-of-rho-gtpase-activity-in-zebrafish
#19
Nicholas J Hanovice, Emily McMains, Jeffrey M Gross
No abstract text is available yet for this article.
June 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28489960/swap70-is-a-universal-gef-like-adapter-for-tethering-actin-to-phagosomes
#20
Maksim V Baranov, Natalia H Revelo, Daniëlle R J Verboogen, Martin Ter Beest, Geert van den Bogaart
We recently identified a key role for SWAP70 as the tethering factor stabilizing F-actin filaments on the surface of phagosomes in human dendritic cells by interacting both with Rho-family GTPases and the lipid phosphatidylinositol (3,4)-bisphosphate. In this study, we aimed to investigate whether this role of SWAP70 was general among immune phagocytes. Our data reveal that SWAP70 is recruited to early phagosomes of macrophages and dendritic cells from both human and mouse. The putative inhibitor of SWAP70 sanguinarine blocked phagocytosis and F-actin polymerization, supporting a key role for SWAP70 in phagocytosis as demonstrated previously with knock-down...
May 10, 2017: Small GTPases
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