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Rho GTPases

P Gómez-Contreras, J M Ramiro-Díaz, A Sierra, C Stipp, F E Domann, R J Weigel, G Lal
ECM1 overexpression is an independent predictor of poor prognosis in primary breast carcinomas, however the mechanisms by which ECM1 affects tumor progression have not been completely elucidated. ECM1 was silenced in the triple-negative breast cancer cell lines Hs578T and MDAMB231 using siRNA and the cells were evaluated for changes in morphology, migration, invasion and adhesion. Actin cytoskeleton alterations were evaluated by fluorescent staining and levels of activated Rho GTPases by pull down assays. ECM1 downregulation led to significantly diminished cell migration (p = 0...
October 21, 2016: Clinical & Experimental Metastasis
Hisateru Komatsu, Tomohiro Iguchi, Takaaki Masuda, Hidenari Hirata, Masami Ueda, Shinya Kidogami, Yushi Ogawa, Kuniaki Sato, Qingjiang Hu, Sho Nambara, Tomoko Saito, Shotaro Sakimura, Ryutaro Uchi, Shuhei Ito, Hidetoshi Eguchi, Keishi Sugimachi, Hidetoshi Eguchi, Yuichiro Doki, Masaki Mori, Koshi Mimori
BACKGROUND: The RND1 gene encodes a protein that belongs to the Rho GTPase family, which regulates various cellular functions. Depletion of RND1 expression activates the oncogenic Ras signaling pathway. In this study, we aimed to clarify the clinical significance of RND1 expression in predicting prognosis and to investigate its biological role in human hepatocellular carcinoma (HCC). METHODS: The association between RND1 expression and clinical outcomes in patients with HCC was analyzed in three independent cohorts: 120 cases resected in our hospital; 370 cases in The Cancer Genome Atlas (TCGA); and 242 cases in GSE14520...
October 21, 2016: Annals of Surgical Oncology
Ana Rolo, Sarah Escuin, Nicholas D E Greene, Andrew J Copp
Neural tube closure is an important morphogenetic event that involves dramatic reshaping of both neural and non-neural tissues. Rho GTPases are key cytoskeletal regulators involved in cell motility and in several developmental processes, and are thus expected to play pivotal roles in neurulation. Here, we discuss 2 recent studies that shed light on the roles of distinct Rho GTPases in different tissues during neurulation. RhoA plays an essential role in regulating actomyosin dynamics in the neural epithelium of the elevating neural folds, while Rac1 is required for the formation of cell protrusions in the non-neural surface ectoderm during neural fold fusion...
October 21, 2016: Small GTPases
Nicole S Nicholas, Aikaterini Pipili, Michaela S Lesjak, Simon M Ameer-Beg, Jenny L C Geh, Ciaran Healy, Alistair D MacKenzie Ross, Maddy Parsons, Frank O Nestle, Katie E Lacy, Claire M Wells
Cancer cells are thought to use actin rich invadopodia to facilitate matrix degradation. Formation and maturation of invadopodia requires the co-ordained activity of Rho-GTPases, however the molecular mechanisms that underlie the invadopodia lifecycle are not fully elucidated. Previous work has suggested a formation and disassembly role for Rho family effector p-21 activated kinase 1 (PAK1) however, related family member PAK4 has not been explored. Systematic analysis of isoform specific depletion using in vitro and in vivo invasion assays revealed there are differential invadopodia-associated functions...
September 27, 2016: Oncotarget
Katsuya Sato, Masashi Kimura, Kazue Sugiyama, Masashi Nishikawa, Yukio Okano, Hitoshi Nagaoka, Takahiro Nagase, Yukio Kitade, Hiroshi Ueda
PLEKHG2/FLJ00018 is a Gβγ-dependent guanine nucleotide exchange factor for the small GTPases Rac and Cdc42 and has been shown to mediate the signaling pathways leading to actin cytoskeleton reorganization. Here we showed that the zinc finger domain-containing protein four-and-a-half LIM domains 1 (FHL1) acts as a novel interaction partner of PLEKHG2 by the yeast two-hybrid system. Among the isoforms of FHL1 (i.e., FHL1A, FHL1B and FHL1C), FHL1A and FHL1B interacted with PLEKHG2. We found that there was an FHL1-binding region at amino acids 58-150 of PLEKHG2...
October 20, 2016: Journal of Biological Chemistry
Soula Danopoulos, Michael Krainock, Omar Toubat, Matthew Thornton, Brendan Grubbs, Denise Al Alam
Lung branching morphogenesis relies on a number of factors, including proper epithelial cell proliferation and differentiation, cell polarity and migration. Rac1, a small Rho GTPase, orchestrates a number of these cellular processes, including cell proliferation and differentiation, cellular alignment and polarization. Furthermore, Rac1 modulates both non-canonical and canonical Wnt signaling, important pathways in lung branching morphogenesis. Culture of embryonic mouse lung explants in the presence of the Rac1 inhibitor (NSC23766) resulted in a dose-dependent decrease in branching...
October 7, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Suxu Tan, Jun Yao, Tao Zhou, Shikai Liu, Zihao Yuan, Changxu Tian, Qi Li, Zhanjiang Liu
The Rho family GTPases are a group of small monomeric G proteins, which are molecular switches in signaling pathways. They have been known to regulate a diverse range of cellular processes including actin cytoskeleton rearrangement and microtubule dynamics. In particular, their participations in immune responses are also significant. However, little information of the Rho GTPases is available in teleost including channel catfish, an economically important species and one of the best teleost models for immune research...
October 17, 2016: Developmental and Comparative Immunology
Mathieu Fonteneau, Dominique Filliol, Patrick Anglard, Katia Befort, Pascal Romieu, Jean Zwiller
DNA methylation is a major epigenetic process which regulates the accessibility of genes to the transcriptional machinery. In the present study, we investigated whether modifying the global DNA methylation pattern in the brain would alter cocaine intake by rats, using the cocaine self-administration test. The data indicate that treatment of rats with the DNA methyltransferase inhibitors 5-aza-2'-deoxycytidine and zebularine actually enhanced the reinforcing properties of cocaine. To get some insights about the underlying neurobiological mechanisms, a genome-wide methylation analysis was undertaken in the prefrontal cortex of rats self-administering cocaine and treated or not with 5-aza-2'-deoxycytidine...
October 20, 2016: Genes, Brain, and Behavior
Anika Steffen, Theresia E B Stradal, Klemens Rottner
The actin cytoskeleton is essential for morphogenesis and virtually all types of cell shape changes. Reorganization is per definition driven by continuous disassembly and re-assembly of actin filaments, controlled by major, ubiquitously operating machines. These are specifically employed by the cell to tune its activities in accordance with respective environmental conditions or to satisfy specific needs.Here we sketch some fundamental signalling pathways established to contribute to the reorganization of specific actin structures at the plasma membrane...
October 19, 2016: Handbook of Experimental Pharmacology
Alexander E Lang, Sonja Kühn, Hans Georg Mannherz
Actin is one of the most abundant cellular proteins and an essential constituent of the actin cytoskeleton, which by its dynamic behavior participates in many cellular activities. The organization of the actin cytoskeleton is regulated by a large number of proteins and represents one of the major targets of bacterial toxins. A number of bacterial effector proteins directly modify actin: Clostridial bacteria produce toxins, which ADP-ribosylate actin at Arg177 leading to inhibition of actin polymerization. The bacterium Photorhabdus luminescens produces several types of protein toxins, including the high molecular weight Tc toxin complex, whose component TccC3 ADP-ribosylates actin at Thr148 promoting polymerization and aggregation of intracellular F-actin leading to inhibition of several cellular functions, such as phagocytosis...
October 19, 2016: Current Topics in Microbiology and Immunology
Sandeep Gopal, Hinke A B Multhaupt, Roger Pocock, John R Couchman
Cell-extracellular matrix (ECM) and cell-cell junctions that employ microfilaments are sites of tension. They are important for tissue repair, morphogenetic movements and can be emblematic of matrix contraction in fibrotic disease and the stroma of solid tumors. One cell surface receptor, syndecan-4, has been shown to regulate focal adhesions, junctions that form at the ends of microfilament bundles in response to matrix components such as fibronectin. Recently it has been shown that signaling emanating from this proteoglycan receptor includes regulation of Rho family GTPases and cytosolic calcium...
October 14, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
Anne Blangy
Tensins are focal adhesion molecules that were identified and characterized in the late 1980's - early 1990's. They play an essential role in the control of cell adhesion. Tensins can bind the tail of ß integrin via their Phospho Tyrosine Binding (PTB) domain, they exhibit various protein interaction domains including a Src Homology 2 (SH2) domain and they are serine-, threonine- and tyrosine-phosphorylated in response to various stimuli. Tensins serve as scaffolds to gather signaling molecules at the extracellular matrix adhesion complexes...
October 17, 2016: Biology of the Cell
Qian Jiao, Li Wang, Zhichao Zhang, Yuanyuan Wang, Hanqi Yan, Wen Ma, Weilin Jin, Haixia Lu, Yong Liu
Different SLIT-ROBO Rho GTPase-activating proteins (srGAPs) have different levels of expression and diverse functions during neural development. Although srGAP2 is expressed in developmental brain tissue, little is known about its influence on cellular development of the nervous system. In the current study, dynamic expression of endogenous srGAP2 during neural stem cell/progenitor cell (NSC/NPC) differentiation in vitro was investigated in order to elucidate the association between the dynamic expression of srGAP2 and neural development...
October 4, 2016: Molecular Medicine Reports
M Wu, M Hamaker, L Li, D Small, A S Duffield
The FMS-like tyrosine kinase-3 (FLT3) gene is the most commonly mutated gene in acute myeloid leukemia (AML), and patients carrying internal tandem duplication (ITD) mutations have a poor prognosis. Long-term inhibition of FLT3 activity in these patients has been elusive. To provide a more complete understanding of FLT3 biology, a mass spectroscopy-based screen was performed to search for FLT3-interacting proteins. The screen identified dedicator of cytokinesis 2 (DOCK2), which is a guanine nucleotide exchange factor for Rho GTPases, and its expression is limited to hematolymphoid cells...
October 17, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Claire-Anne Gutekunst, Jack K Tung, Margaret E McDougal, Robert E Gross
Regrowth inhibitory molecules prevent axon regeneration in the adult mammalian central nervous system (CNS). RhoA, a small GTPase in the Rho family, is a key intracellular switch that mediates the effects of these extracellular regrowth inhibitors. The bacterial enzyme C3-ADP ribosyltransferase (C3) selectively and irreversibly inhibits the activation of RhoA and stimulates axon outgrowth and regeneration. However, effective intracellular delivery of the C3 protein in vivo is limited by poor cell permeability and a short duration of action...
October 13, 2016: Neuroscience
Delyan R Mutavchiev, Marcin Leda, Kenneth E Sawin
The Rho family GTPase Cdc42 is a key regulator of eukaryotic cellular organization and cell polarity [1]. In the fission yeast Schizosaccharomyces pombe, active Cdc42 and associated effectors and regulators (the "Cdc42 polarity module") coordinate polarized growth at cell tips by controlling the actin cytoskeleton and exocytosis [2-4]. Localization of the Cdc42 polarity module to cell tips is thus critical for its function. Here we show that the fission yeast stress-activated protein kinase Sty1, a homolog of mammalian p38 MAP kinase, regulates localization of the Cdc42 polarity module...
October 1, 2016: Current Biology: CB
Emmanuel Lemichez
The virulence of highly pathogenic bacteria such as Salmonella, Yersinia, Staphylococci, Clostridia, and pathogenic strains of Escherichia coli involves intimate cross-talks with the host actin cytoskeleton and its upstream regulators. A large number of virulence factors expressed by these pathogens modulate Rho GTPase activities either by mimicking cellular regulators or by catalyzing posttranslational modifications of these small proteins. This impressive convergence of virulence toward Rho GTPases and actin indeed offers pathogens the capacity to breach host defenses and invade their host, while it promotes inflammatory reactions...
October 16, 2016: Current Topics in Microbiology and Immunology
Nelly Redolfi, Luisa Galla, Andrea Maset, Luca Murru, Eleonora Savoia, Ilaria Zamparo, Angela Gritti, Pierre Billuart, Maria Passafaro, Claudia Lodovichi
Among the X-linked genes associated to intellectual disability, Oligophrenin-1 (OPHN1) encodes for a Rho GTPase-activating protein, a key regulator of several developmental processes, such as dendrite and spine formation and synaptic activity. Inhibitory interneurons play a key role in the development and function of neuronal circuits. Whether mutation of OPHN1 can affect morphology and synaptic properties of inhibitory interneurons remains poorly understood. To address these open questions, we studied in a well established mouse model of X-linked intellectual disability, i...
October 13, 2016: Human Molecular Genetics
Christina Stoeckle, Barbara Geering, Shida Yousefi, Saša Rožman, Nicola Andina, Charaf Benarafa, Hans-Uwe Simon
Eosinophils are frequently elevated in pathological conditions and can cause tissue damage and disease exacerbation. The number of eosinophils in the blood is largely regulated by factors controlling their production in the bone marrow. While several exogenous factors, such as interleukin-5, have been described to promote eosinophil differentiation, comparatively little is known about eosinophil-intrinsic factors that control their de novo generation. Here, we report that the small atypical GTPase RhoH is induced during human eosinophil differentiation, highly expressed in mature blood eosinophils and further upregulated in patients suffering from a hypereosinophilic syndrome...
October 14, 2016: Cell Death and Differentiation
Weiliang Lu, Xixi Wang, Jingjing Liu, Yu He, Ziwei Liang, Zijing Xia, Ying Cai, Liangxue Zhou, Hongxia Zhu, Shufang Liang
The protein ARHGDIA has been found to play distinct roles in cancer progression for several tumors. However, it remains elusive whether and how ARHGDIA plays functions in human glioma. In this study, we discovered that ARHGDIA is much downregulated in human glioma; meanwhile, its expression negatively correlates with glioma malignancy and positively relates to prognosis of glioma patients. It has independent predictive value of ARHGDIA expression level for overall survival of human glioma patients. Glioma patients with ARHGDIA-positive expression have a longer overall survival time than ARHGDIA-negative patients...
October 10, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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