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Rac1 RhoA

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https://www.readbyqxmd.com/read/28339090/inhibition-of-farnesyl-pyrophosphate-synthase-attenuates-high-glucose%C3%A2-induced-vascular-smooth-muscle-cells-proliferation
#1
Guo-Ping Chen, Xiao-Qin Zhang, Tao Wu, Jie Han, Dan Ye
The proliferation of vascular smooth muscle cells (VSMCs) is one of the main features of atherosclerosis accelerated by hyperglycemia. Our previous studies found that farnesyl pyrophosphate synthase (FPPS, EC 2.5.1.10), an essential enzyme in the mevalonate pathway, was upregulated in aorta media from diabetic mice along with the process of atherosclerosis. However, the exact role of FPPS in high glucose‑induced proliferation of VSMCs is largely unclear. In our study, we found that alendronate (an FPPS inhibitor) attenuated diabetic accelerated atherosclerosis in vivo and suppressed high glucose‑induced VSMCs proliferation in vitro...
March 23, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28301477/fragility-of-foot-process-morphology-in-kidney-podocytes-arises-from-chaotic-spatial-propagation-of-cytoskeletal-instability
#2
Cibele V Falkenberg, Evren U Azeloglu, Mark Stothers, Thomas J Deerinck, Yibang Chen, John C He, Mark H Ellisman, James C Hone, Ravi Iyengar, Leslie M Loew
Kidney podocytes' function depends on finger-like projections (foot processes) that interdigitate with those from neighboring cells to form the glomerular filtration barrier. The integrity of the barrier depends on spatial control of dynamics of actin cytoskeleton in the foot processes. We determined how imbalances in regulation of actin cytoskeletal dynamics could result in pathological morphology. We obtained 3-D electron microscopy images of podocytes and used quantitative features to build dynamical models to investigate how regulation of actin dynamics within foot processes controls local morphology...
March 16, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28289332/pi3k%C3%AE-isoform-dependent-activation-of-rhoa-regulates-wnt5a-induced-osteosarcoma-cell-migration
#3
Ailiang Zhang, Ting Yan, Kun Wang, Zhihui Huang, Jinbo Liu
BACKGROUND: We have reported that the phosphatidylinositol-3 kinase (PI3K)/Akt signaling pathway mediated Wnt5a-induced osteosarcoma cell migration. However, the signaling pathways regulating Wnt5a/PI3K/Akt-mediated cell migration remains poorly defined in osteosarcoma cells. METHODS: We evaluated the activations of RhoA, Rac1 and Cdc42 in osteosarcoma MG-63 and U2OS cells with small G-protein activation assay. Boyden chamber assays were used to confirm the migration of cells transfected indicated constructs or siRNA specific against RhoA...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28287327/mechanism-of-cell-intrinsic-adaptation-to-adams-oliver-syndrome-gene-dock6-disruption-highlights-ubiquitin-like-modifier-isg15-as-a-regulator-of-rho-gtpases
#4
Berati Cerikan, Elmar Schiebel
DOCK6 is a RAC1/CDC42 guanine nucleotide exchange factor, however, little is known about its function and sub-cellular localization. DOCK6 regulates the balance between RAC1 and RHOA activity during cell adhesion and is important for CDC42-dependent mitotic chromosome alignment. Surprisingly, a cell intrinsic adaptation mechanism compensates for errors in these DOCK6 functions that arise as a consequence of prolonged DOCK6 depletion or complete removal in DOCK6 knockout cells. Down-regulation of the ubiquitin-like modifier ISG15 accounts for this adaptation...
February 23, 2017: Small GTPases
https://www.readbyqxmd.com/read/28238662/coordination-by-cdc42-of-actin-contractility-and-adhesion-for-melanoblast-movement-in-mouse-skin
#5
Emma F Woodham, Nikki R Paul, Benjamin Tyrrell, Heather J Spence, Karthic Swaminathan, Michelle R Scribner, Evangelos Giampazolias, Ann Hedley, William Clark, Frieda Kage, Daniel J Marston, Klaus M Hahn, Stephen W G Tait, Lionel Larue, Cord H Brakebusch, Robert H Insall, Laura M Machesky
The individual molecular pathways downstream of Cdc42, Rac, and Rho GTPases are well documented, but we know surprisingly little about how these pathways are coordinated when cells move in a complex environment in vivo. In the developing embryo, melanoblasts originating from the neural crest must traverse the dermis to reach the epidermis of the skin and hair follicles. We previously established that Rac1 signals via Scar/WAVE and Arp2/3 to effect pseudopod extension and migration of melanoblasts in skin...
March 6, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28235899/dual-targeting-of-mesenchymal-and-amoeboid-motility-hinders-metastatic-behavior
#6
Brandon C Jones, Laura C Kelley, Yuriy V Loskutov, Kristina M Marinak, Varvara K Kozyreva, Matthew B Smolkin, Elena N Pugacheva
Commonly upregulated in human cancers, the scaffolding protein NEDD9/HEF1 is a known regulator of mesenchymal migration and cancer cell plasticity. However, the functional role of NEDD9 as a regulator of different migration/invasion modes in the context of breast cancer metastasis is currently unknown. Here, it is reported that NEDD9 is necessary for both mesenchymal and amoeboid individual cell migration/invasion in triple-negative breast cancer (TNBC). NEDD9 deficiency results in acquisition of the amoeboid morphology, but severely limits all types of cell motility...
February 24, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28231640/mind-the-gap-mechanisms-regulating-the-endothelial-barrier
#7
REVIEW
Mariya Y Radeva, Jens Waschke
The endothelial barrier consists of intercellular contacts localized in the cleft between endothelial cells, which is covered by the glycocalyx in a sieve-like manner. Both types of barrier-forming junctions, i.e. the adherens junction (AJ) serving mechanical anchorage and mechanotransduction and the tight junction (TJ) sealing the intercellular space to limit paracelullar permeability, are tethered to the actin cytoskeleton. Under resting conditions, the endothelium thereby builds a selective layer controlling the exchange of fluid and solutes with the surrounding tissue...
February 23, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28214467/paxillin-a-crossroad-in-pathological-cell-migration
#8
REVIEW
Ana María López-Colomé, Irene Lee-Rivera, Regina Benavides-Hidalgo, Edith López
Paxilllin is a multifunctional and multidomain focal adhesion adapter protein which serves an important scaffolding role at focal adhesions by recruiting structural and signaling molecules involved in cell movement and migration, when phosphorylated on specific Tyr and Ser residues. Upon integrin engagement with extracellular matrix, paxillin is phosphorylated at Tyr31, Tyr118, Ser188, and Ser190, activating numerous signaling cascades which promote cell migration, indicating that the regulation of adhesion dynamics is under the control of a complex display of signaling mechanisms...
February 18, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28196833/characterization-of-the-activation-of-small-gtpases-by-their-gefs-on-membranes-using-artificial-membrane-tethering
#9
François Peurois, Simon Veyron, Yann Ferrandez, Ilham Ladid, Sarah Benabdi, Mahel Zeghouf, Gérald Peyroche, Jacqueline Cherfils
Attachment of active, GTP-bound small GTPases to membranes by post-translational lipid modifications is pivotal for their ability to process and propagate information in cells. However, generating and manipulating lipidated GTPases has remained difficult, which has limited our quantitative understanding of their activation by GEFs and their termination by GAPs. Here we replaced the lipid modification by a histidine tag in eleven full-length, human small GTPases belonging to the Arf, Rho and Rab families, which allowed to tether them to nickel-lipid containing membranes and characterize the kinetics of their activation by GEFs...
February 14, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28196303/the-long-noncoding-rna-schlah-suppresses-metastasis-of-hepatocellular-carcinoma-through-interacting-with-fus
#10
Zhouhong Ge, Zhuoan Cheng, Xinrong Yang, Xisong Huo, Ning Wang, Hui Wang, Cun Wang, Dishui Gu, Fangyu Zhao, Ming Yao, Jia Fan, Wenxin Qin
Emerging evidence has indicated that deregulation of long non-coding RNAs (lncRNAs) can contribute to the progression and metastasis of human cancer, including hepatocellular carcinoma (HCC). However, the roles of most lncRNAs in HCC remain largely unknown. Here we found a long noncoding RNA termed SchLAH (seven chromosome locus associated with HCC; also called BC035072) was generally downregulated in HCC. Low expression of SchLAH was significantly correlated with shorter overall survival of HCC patients. In vitro and in vivo assays indicated that overexpression of SchLAH inhibited the migration and lung metastasis of HCC cells...
February 14, 2017: Cancer Science
https://www.readbyqxmd.com/read/28188861/functions-of-rho-family-of-small-gtpases-and-rho-associated-coiled-coil-kinases-in-bone-cells-during-differentiation-and-mineralization
#11
REVIEW
Agnieszka Strzelecka-Kiliszek, Saida Mebarek, Monika Roszkowska, René Buchet, David Magne, Slawomir Pikula
BACKGROUND: Members of Rho-associated coiled-coil kinases (ROCKs) are effectors of Rho family of small GTPases. ROCKs have multiple functions that include regulation of cellular contraction and polarity, adhesion, motility, proliferation, apoptosis, differentiation, maturation and remodeling of the extracellular matrix (ECM). SCOPE OF THE REVIEW: Here, we focus on the action of RhoA and RhoA effectors, ROCK1 and ROCK2, in cells related to tissue mineralization: mesenchymal stem cells, chondrocytes, preosteoblasts, osteoblasts, osteocytes, lining cells and osteoclasts...
February 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28161375/receptor-stimulated-transamidation-induces-activation-of-rac1-and-cdc42-and-the-regulation-of-dendritic-spines
#12
Zhen Mi, Tuda Si, Khushboo Kapadia, Qian Li, Nancy A Muma
Regulation of dendritic spines is an important component of synaptic function and plasticity whereas dendritic spine dysregulation is related to several psychiatric and neurological diseases. In the present study, we tested the hypothesis that serotonin (5-HT)2A/2C receptor-induced Rho family transamidation and activation regulates dendritic spine morphology and that activation of multiple types of receptors can induce transglutaminase (TGase)-catalyzed transamidation of small G proteins. We previously reported a novel 5-HT2A receptor downstream effector, TGase-catalyzed serotonylation of the small G protein Rac1 in A1A1v cells, a rat embryonic cortical cell line...
February 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28154894/actin-dynamics-in-the-regulation-of-endothelial-barrier-functions-and-neutrophil-recruitment-during-endotoxemia-and-sepsis
#13
REVIEW
Michael Schnoor, Alexander García Ponce, Eduardo Vadillo, Rosana Pelayo, Jan Rossaint, Alexander Zarbock
Sepsis is a leading cause of death worldwide. Increased vascular permeability is a major hallmark of sepsis. Dynamic alterations in actin fiber formation play an important role in the regulation of endothelial barrier functions and thus vascular permeability. Endothelial integrity requires a delicate balance between the formation of cortical actin filaments that maintain endothelial cell contact stability and the formation of actin stress fibers that generate pulling forces, and thus compromise endothelial cell contact stability...
February 2, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28152068/aerobic-exercise-regulates-rho-cofilin-pathways-to-rescue-synaptic-loss-in-aged-rats
#14
Yan Li, Li Zhao, Boya Gu, Jiajia Cai, Yuanyuan Lv, Laikang Yu
PURPOSE: The role of exercise to prevent or reverse aging-induced cognitive decline has been widely reported. This neuroprotection is associated with changes in the synaptic structure plasticity. However, the mechanisms of exercise-induced synaptic plasticity in the aging brain are still unclear. Thus, the aim of the present study is to investigate the aging-related alterations of Rho-GTPase and the modulatory influences of exercise training. METHODS: Young and old rats were used in this study...
2017: PloS One
https://www.readbyqxmd.com/read/28148498/assessment-of-roles-for-the-rho-specific-guanine-nucleotide-dissociation-inhibitor-rhogdi-ly-gdi-in-platelet-function-a-spatial-systems-approach
#15
Anh T P Ngo, Marisa L D Thierheimer, Özgün Babur, Anne D Rocheleau, Tao Huang, Jiaqing Pang, Rachel A Rigg, Annachiara Mitrugno, Dan Theodorescu, Julja Burchard, Xiaolin Nan, Emek Demir, Owen J T McCarty, Joseph E Aslan
Upon activation at sites of vascular injury, platelets undergo morphological alterations essential to hemostasis via cytoskeletal reorganizations driven by the Rho GTPases Rac1, Cdc42 and RhoA. Here we investigate roles for Rho-specific guanine nucleotide dissociation inhibitor proteins (RhoGDIs) in platelet function. We find that platelets express two RhoGDI family members, RhoGDI and Ly-GDI. While RhoGDI localizes throughout platelets in a granule-like manner, Ly-GDI shows an asymmetric, polarized localization that largely overlaps with Rac1 and Cdc42 as well as microtubules and protein kinase C (PKC) in platelets adherent to fibrinogen...
February 1, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28129038/regulation-of-small-gtpase-activity-by-g1-cyclins
#16
Neus Pedraza, Tània Cemeli, Ma Ventura Monserrat, Eloi Garí, Francisco Ferrezuelo
Together with a cyclin-dependent kinase (CDK) partner G1 cyclins control cell cycle entry by phosphorylating a number of nuclear targets and releasing a transcriptional program at the end of G1 phase. Yeast G1 cyclins also operate on cytoplasmic targets involved in the polarization of the cytoskeleton and vesicle trafficking. These processes are mainly controlled by the small GTPase Cdc42, and G1 cyclins regulate the activity of this and other small GTPases through the modulation of their regulators and effectors...
January 27, 2017: Small GTPases
https://www.readbyqxmd.com/read/28114951/hiv-signaling-through-cd4-and-ccr5-activates-rho-family-gtpases-that-are-required-for-optimal-infection-of-primary-cd4-t-cells
#17
Mark B Lucera, Zach Fleissner, Caroline O Tabler, Daniela M Schlatzer, Zach Troyer, John C Tilton
BACKGROUND: HIV-1 hijacks host cell machinery to ensure successful replication, including cytoskeletal components for intracellular trafficking, nucleoproteins for pre-integration complex import, and the ESCRT pathway for assembly and budding. It is widely appreciated that cellular post-translational modifications (PTMs) regulate protein activity within cells; however, little is known about how PTMs influence HIV replication. Previously, we reported that blocking deacetylation of tubulin using histone deacetylase inhibitors promoted the kinetics and efficiency of early post-entry viral events...
January 24, 2017: Retrovirology
https://www.readbyqxmd.com/read/28114311/rhogtpase-regulators-orchestrate-distinct-stages-of-synaptic-development
#18
Samuel Martin-Vilchez, Leanna Whitmore, Hannelore Asmussen, Jessica Zareno, Rick Horwitz, Karen Newell-Litwa
Small RhoGTPases regulate changes in post-synaptic spine morphology and density that support learning and memory. They are also major targets of synaptic disorders, including Autism. Here we sought to determine whether upstream RhoGTPase regulators, including GEFs, GAPs, and GDIs, sculpt specific stages of synaptic development. The majority of examined molecules uniquely regulate either early spine precursor formation or later maturation. Specifically, an activator of actin polymerization, the Rac1 GEF β-PIX, drives spine precursor formation, whereas both FRABIN, a Cdc42 GEF, and OLIGOPHRENIN-1, a RhoA GAP, regulate spine precursor elongation...
2017: PloS One
https://www.readbyqxmd.com/read/28109909/erk2-zeb1-mir-101-1-axis-contributes-to-epithelial-mesenchymal-transition-and-cell-migration-in-cancer
#19
Kailash Chandra Mangalhara, Siddharth Manvati, Sunil Kumar Saini, Kalaiarasan Ponnusamy, Gaurav Agarwal, Suresh K Abraham, Rameshwar N K Bamezai
Regulation of metastasis continues to remain enigmatic despite our improved understanding of cancer. Identification of microRNAs associated with metastasis in the recent past has provided a new hope. Here, we show how microRNA-101 (miR-101) regulates two independent processes of cellular metastasis by targeting pro-metastatic upstream regulatory transcription factors, ZEB1 and ZEB2, and downstream effector-actin modulators, RHOA and RAC1, providing a single target for therapeutic intervention. Further, we depict how down-regulation of miR-101 by extracellular signal-regulated kinase-2 (ERK2) is vital for MAP kinase pathway induced cellular migration and mesenchymal transition...
January 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28068967/enterolactone-alters-fak-src-signaling-and-suppresses-migration-and-invasion-of-lung-cancer-cell-lines
#20
Shireen Chikara, Kaitlin Lindsey, Pawel Borowicz, Melpo Christofidou-Solomidou, Katie M Reindl
BACKGROUND: Systemic toxicity of chemotherapeutic agents and the challenges associated with targeting metastatic tumors are limiting factors for current lung cancer therapeutic approaches. To address these issues, plant-derived bioactive components have been investigated for their anti-cancer properties because many of these agents are non-toxic to healthy tissues. Enterolactone (EL) is a flaxseed-derived mammalian lignan that has demonstrated anti-migratory properties for various cancers, but EL has not been investigated in the context of lung cancer, and its anticancer mechanisms are ill-defined...
January 9, 2017: BMC Complementary and Alternative Medicine
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