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Rac1 RhoA

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https://www.readbyqxmd.com/read/27913679/modelling-gtpase-dynamics-to-understand-rhoa-driven-cancer-cell-invasion
#1
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/27892530/fine-tuning-of-rac1-and-rhoa-alters-cuspal-shapes-by-remolding-the-cellular-geometry
#2
Liwen Li, Qinghuang Tang, Takashi Nakamura, Jun-Gyo Suh, Hayato Ohshima, Han-Sung Jung
The anatomic and functional combinations of cusps and lophs (ridges) define the tooth shape of rodent molars, which distinguishes species. The species-specific cusp patterns result from the spatiotemporal induction of enamel knots (EKs), which require precisely controlled cellular behavior to control the epithelial invagination. Despite the well-defined roles of EK in cusp patterning, the determinants of the ultimate cuspal shapes and involvement of epithelial cellular geometry are unknown. Using two typical tooth patterns, the lophodont in gerbils and the bunodont in mice, we showed that the cuspal shape is determined by the dental epithelium at the cap stage, whereas the cellular geometry in the inner dental epithelium (IDE) is correlated with the cuspal shape...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27852748/quantitative-gtpase-affinity-purification-identifies-rho-family-protein-interaction-partners
#3
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
#4
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/27827394/mitochondrial-ca-2-uptake-controls-actin-cytoskeleton-dynamics-during-cell-migration
#5
Julien Prudent, Nikolay Popgeorgiev, Rudy Gadet, Mathieu Deygas, Ruth Rimokh, Germain Gillet
Intracellular Ca(2+) signaling regulates cell migration by acting on cytoskeleton architecture, cell directionality and focal adhesions dynamics. In migrating cells, cytosolic Ca(2+) pool and Ca(2+) pulses are described as key components of these effects. Whereas the role of the mitochondrial calcium homeostasis and the Mitochondria Cacium Uniporter (MCU) in cell migration were recently highlighted in vivo using the zebrafish model, their implication in actin cystokeleton dynamics and cell migration in mammals is not totally characterized...
November 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27821782/rac1-rhoa-antagonism-defines-cell-to-cell-heterogeneity-during-epidermal-morphogenesis-in-nematodes
#6
Emmanuel Martin, Marie-Hélène Ouellette, Sarah Jenna
The antagonism between the GTPases Rac1 and RhoA controls cell-to-cell heterogeneity in isogenic populations of cells in vitro and epithelial morphogenesis in vivo Its involvement in the regulation of cell-to-cell heterogeneity during epidermal morphogenesis has, however, never been addressed. We used a quantitative cell imaging approach to characterize epidermal morphogenesis at a single-cell level during early elongation of Caenorhabditis elegans embryos. This study reveals that a Rac1-like pathway, involving the Rac/Cdc42 guanine-exchange factor β-PIX/PIX-1 and effector PAK1/PAK-1, and a RhoA-like pathway, involving ROCK/LET-502, control the remodeling of apical junctions and the formation of basolateral protrusions in distinct subsets of hypodermal cells...
November 7, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27798233/cd44-a-novel-synaptic-cell-adhesion-molecule-regulating-structural-and-functional-plasticity-of-dendritic-spines
#7
Matylda Roszkowska, Anna Skupien, Tomasz Wójtowicz, Anna Konopka, Adam Gorlewicz, Magdalena Kisiel, Marek Bekisz, Blazej Ruszczycki, Hubert Dolezyczek, Emilia Rejmak, Ewelina Knapska, Jerzy W Mozrzymas, Jakub Wlodarczyk, Grzegorz M Wilczynski, Joanna Dzwonek
Synaptic cell adhesion molecules regulate signal transduction, synaptic function, and plasticity. However, their role in neuronal interactions with the extracellular matrix (ECM) is not well understood. Here, we report that the CD44, a transmembrane receptor for hyaluronan, modulates synaptic plasticity. The performed high-resolution ultrastructural analysis showed that CD44 was localized at mature synapses in the adult brain. The diminished expression of CD44 affected the synaptic excitatory transmission of primary hippocampal neurons, simultaneously modifying dendritic spine shape...
October 19, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27795403/the-andes-virus-nucleocapsid-protein-directs-basal-endothelial-cell-permeability-by-activating-rhoa
#8
Elena E Gorbunova, Matthew J Simons, Irina N Gavrilovskaya, Erich R Mackow
: Andes virus (ANDV) predominantly infects microvascular endothelial cells (MECs) and nonlytically causes an acute pulmonary edema termed hantavirus pulmonary syndrome (HPS). In HPS patients, virtually every pulmonary MEC is infected, MECs are enlarged, and infection results in vascular leakage and highly lethal pulmonary edema. We observed that MECs infected with the ANDV hantavirus or expressing the ANDV nucleocapsid (N) protein showed increased size and permeability by activating the Rheb and RhoA GTPases...
October 25, 2016: MBio
https://www.readbyqxmd.com/read/27770633/polymer-fiber-based-models-of-connective-tissue-repair-and-healing
#9
Nancy M Lee, Cevat Erisken, Thomas Iskratsch, Michael Sheetz, William N Levine, Helen H Lu
Physiologically relevant models of wound healing are essential for understanding the biology of connective tissue repair and healing. They can also be used to identify key cellular processes and matrix characteristics critical for the design of soft tissue grafts. Modeling the various stages of repair post tendon injury, polymer meshes of varying fiber diameter (nano-1 (390 nm) < nano-2 (740 nm) < micro (1420 nm)) were produced. Alignment was also introduced in the nano-2 group to model matrix undergoing biological healing rather than scar formation...
October 12, 2016: Biomaterials
https://www.readbyqxmd.com/read/27768516/rho-gtpases-in-mammalian-spinal-neural-tube-closure
#10
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
https://www.readbyqxmd.com/read/27761803/the-pivotal-role-of-ccn2-in-mammalian-palatogenesis
#11
Joseph T Tarr, Timothy G Visser, Joanne E Moon, Honey Hendesi, Mary F Barbe, James P Bradley, Steven N Popoff
Mammalian palatogenesis is a complex process involving a temporally and spatially regulated myriad of factors. Together these factors control the 3 vital processes of proliferation, elevation and fusion of the developing palate. In this study, we show for the first time the unequivocally vital role of CCN2 in development of the mammalian palate. We utilized CCN2 knockout (KO) mice and cranial neural crest derived mesenchymal cells from these CCN2 KO mice to investigate the 3 processes crucial to normal palatogenesis...
October 20, 2016: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/27754741/arf6-and-its-zeb1-epb41l5-mesenchymal-axis-are-required-for-both-mesenchymal-and-amoeboid-type-invasion-of-cancer-cells
#12
Haruka Handa, Ari Hashimoto, Shigeru Hashimoto, Hisataka Sabe
Modes of cancer invasion interchange between the mesenchymal type and amoeboid type in response to the microenvironment, in which RhoA and Rac1 are selectively required to perform different modes of actin-cytoskeletal remodeling. Membrane remodeling is another integral part of invasion. Arf6 regulates the recycling of molecules at the cell periphery, and is often overexpressed in malignant cancers together with its effector AMAP1/ASAP1/DDEF1. This pathway promotes mesenchymal-type invasion when AMAP1 binds to EPB41L5, a mesenchymal-specific protein induced by ZEB1...
October 18, 2016: Small GTPases
https://www.readbyqxmd.com/read/27729281/ganglioside-gm3-mediates-glucose-induced-suppression-of-igf-1-receptor-rac1-activation-to-inhibit-keratinocyte-motility
#13
Duncan Hieu M Dam, Xiao-Qi Wang, Sarah Sheu, Mahima Vijay, Desmond Shipp, Luke Miller, Amy S Paller
Activation of insulin-like growth factor-1 (IGF-1) receptor (IGF1R) signaling induces keratinocyte migration, but little is known about its regulation, including in diabetic wounds. GM3, a lipid raft ganglioside synthesized by GM3 synthase (GM3S), regulates receptor signaling. In diabetic mice, knockout or topically-applied nanoconstruct-mediated knockdown of GM3S promotes wound edge IGF1R phosphorylation and re-epithelialization. Through modulating GM3 expression, we explored the role of GM3 in regulating human keratinocyte IGF1R signaling...
October 8, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27726098/downregulation-of-arhgdia-contributes-to-human-glioma-progression-through-activation-of-rho-gtpase-signaling-pathway
#14
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
https://www.readbyqxmd.com/read/27715394/orphan-g-protein-coupled-receptor-gprc5a-modulates-integrin-%C3%AE-1-mediated-epithelial-cell-adhesion
#15
Daria R Bulanova, Yevhen A Akimov, Anne Rokka, Teemu D Laajala, Tero Aittokallio, Petri Kouvonen, Teijo Pellinen, Sergey G Kuznetsov
G-Protein Coupled Receptor (GPCR), Class C, Group 5, Member A (GPRC5A) has been implicated in several malignancies. The underlying mechanisms, however, remain poorly understood. Using a panel of human cell lines, we demonstrate that CRISPR/Cas9-mediated knockout and RNAi-mediated depletion of GPRC5A impairs cell adhesion to integrin substrates: collagens I and IV, fibronectin, as well as to extracellular matrix proteins derived from the Engelbreth-Holm-Swarm (EHS) mouse sarcoma (Matrigel). Consistent with the phenotype, knock-out of GPRC5A correlated with a reduced integrin β1 (ITGB1) protein expression, impaired phosphorylation of the focal adhesion kinase (FAK), and lower activity of small GTPases RhoA and Rac1...
October 7, 2016: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/27715393/expression-of-kindlin-3-in-melanoma-cells-impedes-cell-migration-and-metastasis
#16
Chen Feng, Wei-Kiat Wee, Huizhi Chen, Li-Teng Ong, Jing Qu, Hui-Foon Tan, Suet-Mien Tan
Kindlins are a small family of 4.1-ezrin-radixin-moesin (FERM)-containing cytoplasmic proteins. Kindlin-3 is expressed in platelets, hematopoietic cells, and endothelial cells. Kindlin-3 promotes integrin activation, clustering and outside-in signaling. Aberrant expression of kindlin-3 was reported in melanoma and breast cancer. Intriguingly, kindlin-3 has been reported to either positively or negatively regulate cancer cell metastasis. In this study, we sought to clarify the expression of kindlin-3 in melanoma cells and its role in melanoma metastasis...
October 7, 2016: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/27697549/a-human-cellular-system-for-analyzing-signaling-during-corneal-endothelial-barrier-dysfunction
#17
Diana Santander-García, María Cristina Ortega, Silvia Benito-Martínez, Susana Barroso, Ignacio Jiménez-Alfaro, Jaime Millán
Correct corneal endothelial barrier function is essential for maintaining corneal transparency. However, research on cell signaling pathways mediating corneal endothelial barrier dysfunction has progressed more slowly than that involving other cellular barriers because of the lack of human corneal endothelial cell models. Here we have optimized the culture of the human corneal endothelial cell (HCEC) line B4G12 as a model for studying paracellular permeability. We show that B4G12-HCECs form confluent monolayers with stable cell-cell junctions when cultured on plastic, but not glass, surfaces precoated with various extracellular matrix components...
September 30, 2016: Experimental Eye Research
https://www.readbyqxmd.com/read/27697106/gpr78-promotes-lung-cancer-cell-migration-and-metastasis-by-activation-of-g%C3%AE-q-rho-gtpase-pathway
#18
Dan-Dan Dong, Hui Zhou, Gao Li
GPR78 is an orphan G-protein coupled receptor (GPCR) that is predominantly expressed in human brain tissues. Currently, the function of GPR78 is unknown. In this study, we found that GPR78 was expressed in lung cancer cells and functioned as a novel regulator of lung cancer cell migration and metastasis. We found that knockdown of GPR78 in lung cancer cells suppressed cell migration. Moreover, GPR78 modulated the formation of actin stress fibers in A549 cells in a RhoA- and Rac1-dependent manner. At a molecular level, GPR78 regulated cell motility through the activation of Gαq-RhoA/Rac1 pathway...
September 29, 2016: BMB Reports
https://www.readbyqxmd.com/read/27681226/rhoa-and-rac1-gtpases-differentially-regulate-agonist-receptor-mediated-reactive-oxygen-species-generation-in-platelets
#19
Huzoor Akbar, Xin Duan, Saima Saleem, Ashley K Davis, Yi Zheng
Agonist induced generation of reactive oxygen species (ROS) by NADPH oxidases (NOX) enhances platelet aggregation and hence the risk of thrombosis. RhoA and Rac1 GTPases are involved in ROS generation by NOX in a variety of cells, but their roles in platelet ROS production remain unclear. In this study we used platelets from RhoA and Rac1 conditional knockout mice as well as human platelets treated with Rhosin and NSC23767, rationally designed small molecule inhibitors of RhoA and Rac GTPases, respectively, to better define the contributions of RhoA and Rac1 signaling to ROS generation and platelet activation...
2016: PloS One
https://www.readbyqxmd.com/read/27680697/rho-gtpase-complementation-underlies-bdnf-dependent-homo-and-heterosynaptic-plasticity
#20
Nathan G Hedrick, Stephen C Harward, Charles E Hall, Hideji Murakoshi, James O McNamara, Ryohei Yasuda
The Rho GTPase proteins Rac1, RhoA and Cdc42 have a central role in regulating the actin cytoskeleton in dendritic spines, thereby exerting control over the structural and functional plasticity of spines and, ultimately, learning and memory. Although previous work has shown that precise spatiotemporal coordination of these GTPases is crucial for some forms of cell morphogenesis, the nature of such coordination during structural spine plasticity is unclear. Here we describe a three-molecule model of structural long-term potentiation (sLTP) of murine dendritic spines, implicating the localized, coincident activation of Rac1, RhoA and Cdc42 as a causal signal of sLTP...
September 28, 2016: Nature
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