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Rho GTPase

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https://www.readbyqxmd.com/read/28453519/homozygous-arhgef2-mutation-causes-intellectual-disability-and-midbrain-hindbrain-malformation
#1
Ethiraj Ravindran, Hao Hu, Scott A Yuzwa, Luis R Hernandez-Miranda, Nadine Kraemer, Olaf Ninnemann, Luciana Musante, Eugen Boltshauser, Detlev Schindler, Angela Hübner, Hans-Christian Reinecker, Hans-Hilger Ropers, Carmen Birchmeier, Freda D Miller, Thomas F Wienker, Christoph Hübner, Angela M Kaindl
Mid-hindbrain malformations can occur during embryogenesis through a disturbance of transient and localized gene expression patterns within these distinct brain structures. Rho guanine nucleotide exchange factor (ARHGEF) family members are key for controlling the spatiotemporal activation of Rho GTPase, to modulate cytoskeleton dynamics, cell division, and cell migration. We identified, by means of whole exome sequencing, a homozygous frameshift mutation in the ARHGEF2 as a cause of intellectual disability, a midbrain-hindbrain malformation, and mild microcephaly in a consanguineous pedigree of Kurdish-Turkish descent...
April 28, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28443208/roles-of-rap1-signaling-in-tumor-cell-migration-and-invasion
#2
Yi-Lei Zhang, Ruo-Chen Wang, Ken Cheng, Brian Z Ring, Li Su
Ras-associated protein-1 (Rap1), a small GTPase in the Ras-related protein family, is an important regulator of basic cellular functions (e.g., formation and control of cell adhesions and junctions), cellular migration, and polarization. Through its interaction with other proteins, Rap1 plays many roles during cell invasion and metastasis in different cancers. The basic function of Rap1 is straightforward; it acts as a switch during cellular signaling transduction and regulated by its binding to either guanosine triphosphate (GTP) or guanosine diphosphate (GDP)...
February 2017: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/28438902/crucial-role-of-rock2-mediated-phosphorylation-and-upregulation-of-fhod3-in-the-pathogenesis-of-angiotensin-ii-induced-cardiac-hypertrophy
#3
Qing Zhou, Si-Si Wei, Hong Wang, Qian Wang, Wei Li, Gang Li, Jian-Wen Hou, Xiao-Meng Chen, Jie Chen, Wei-Ping Xu, Yi-Gang Li, Yue-Peng Wang
Cardiac hypertrophy is characterized by increased myofibrillogenesis. Angiotensin II (Ang-II) is an essential mediator of the pressure overload-induced cardiac hypertrophy in part through RhoA/ROCK (small GTPase/Rho-associated coiled-coil containing protein kinase) pathway. FHOD3 (formin homology 2 domain containing 3), a cardiac-restricted member of diaphanous-related formins, is crucial in regulating myofibrillogenesis in cardiomyocytes. FHOD3 maintains inactive through autoinhibition by an intramolecular interaction between its C- and N-terminal domains...
April 24, 2017: Hypertension
https://www.readbyqxmd.com/read/28432431/initial-cell-adhesion-of-three-cell-types-in-the-presence-and-absence-of-serum-proteins
#4
Martina Verdanova, Pavla Sauerova, Ute Hempel, Marie Hubalek Kalbacova
With the development of a wide range of new biomaterials for the sensing of different cell behaviour, it is important to consider whether the cells tested in vitro are in direct contact with the material or whether cell-biomaterial contact is mediated by an interfacial layer of proteins originating from the culture medium or from the cells themselves. Thus, this study describes the differences between the cell adhesion mediated by proteins originating from foetal bovine serum and without the presence of such proteins 2 h following cell seeding exemplarily with different cell types (an osteoblastic cell line, primary fibroblasts, and mesenchymal stem cells)...
April 21, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28429038/-phosphodiesterase-4-inhibition-for-treatment-of-endothelial-barrier-and-microcirculation-disorders-in-sepsis
#5
REVIEW
J Wollborn, N Schlegel, M A Schick
Sepsis is commonly associated with loss of microvascular endothelial barrier function (capillary leak) and dysfunctional microcirculation, which both promote organ failure. The development of a distinct therapy of impaired endothelial barrier function and disturbed microcirculation is highly relevant because both of these phenomena constitute crucial processes which critically influence the prognosis of patients. Numerous in vivo and in vitro trials over the past years have fostered a better understanding of the pathophysiology of capillary leak...
April 20, 2017: Der Anaesthesist
https://www.readbyqxmd.com/read/28423648/polyisoprenylated-cysteinyl-amide-inhibitors-disrupt-actin-cytoskeleton-organization-induce-cell-rounding-and-block-migration-of-non-small-cell-lung-cancer
#6
Elizabeth Ntantie, Jerrine Fletcher, Felix Amissah, Olufisayo O Salako, Augustine T Nkembo, Rosemary A Poku, Francis O Ikpatt, Nazarius S Lamango
The malignant potential of Non-Small Cell Lung Cancer (NSCLC) is dependent on cellular processes that promote metastasis. F-actin organization is central to cell migration, invasion, adhesion and angiogenesis, processes involved in metastasis. F-actin remodeling is enhanced by the overexpression and/or hyper-activation of some members of the Rho family of small GTPases. Therefore, agents that mitigate hyperactive Rho proteins may be relevant for controlling metastasis. We previously reported the role of polyisoprenylated cysteinyl amide inhibitors (PCAIs) as potential inhibitors of cancers with hyperactive small GTPases...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417530/rhogdi%C3%AE-%C3%A2-is%C3%A2-a%C3%A2-potential%C3%A2-prognostic%C3%A2-biomarker%C3%A2-and%C3%A2-controls%C3%A2-telomere-regulation%C3%A2-in%C3%A2-colorectal%C3%A2-cancer
#7
Dandan Huang, Weisi Lu, Shaomin Zou, Huaiming Wang, Yuanling Jiang, Xiya Zhang, Pengqing Li, Zhou Songyang, Lei Wang, Jianping Wang, Junjiu Huang, Lekun Fang
RhoGDIα is an essential regulator for Rho GTPases. Although RhoGDIα may serve as an oncogene in colorectal cancer (CRC), the underlying mechanism is still unclear. Here,we investigate the function, mechanism, and clinical significance of RhoGDIα in CRC progression. We founded that downregulation of RhoGDIα repressed CRC cell proliferation, motility and invasion. Overexpression of RhoGDIα increased DNA damage response signals at telomeres, and led to telomere shortening in CRC cells, also being validated in 26 pairs of CRC tissues...
April 17, 2017: Cancer Science
https://www.readbyqxmd.com/read/28415790/hyperglycemia-via-activation-of-thromboxane-a2-receptor-impairs-the-integrity-and-function-of-blood-brain-barrier-in-microvascular-endothelial-cells
#8
Zhihong Zhao, Jue Hu, Xiaoping Gao, Hui Liang, Haiya Yu, Suosi Liu, Zhan Liu
Diabetes is one of high risk factors for cardio- and cerebra-vascular diseases, including stroke, atherosclerosis and hypertension. This study was conducted to elucidate whether and how thromboxane receptor (TPr) activation contributes to blood-brain barrier (BBB) dysfunction in diabetes. Human brain microvascular endothelial cells (HBMECs) were cultured. The levels of phosphorylated endothelial nitric oxide synthase (eNOS) at Ser1177 (p-eNOS) and Akt at Ser473 (p-Akt) were assayed by western blot. Exposure of HBMECs to either high glucose (HG) or thromboxane A2 (TxA2) mimetic U46619, significantly reduced p-eNOS and p-Akt...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414040/sars-coronavirus-papain-like-protease-up-regulates-the-collagen-expression-through-non-samd-tgf-%C3%AE-1-signaling
#9
Ching-Ying Wang, Chien-Yi Lu, Shih-Wen Li, Chien-Chen Lai, Chun-Hung Hua, Su-Hua Huang, Ying-Ju Lin, Mann-Jen Hour, Cheng-Wen Lin
SARS coronavirus (CoV) papain-like protease (PLpro) reportedly induced the production of TGF-β1 through p38 MAPK/STAT3-meidated Egr-1-dependent activation (Sci. Rep. 6, 25754). This study investigated the correlation of PLpro-induced TGF-β1 with the expression of Type I collagen in human lung epithelial cells and mouse pulmonary tissues. Specific inhibitors for TGF-βRI, p38 MAPK, MEK, and STAT3 proved that SARS-CoV PLpro induced TGF-β1-dependent up-regulation of Type I collagen in vitro and in vivo. Subcellular localization analysis of SMAD3 and SMAD7 indicated that non-SMAD pathways in TGF-β1 signaling involved in the production of Type I collagen in transfected cells with pSARS-PLpro...
April 13, 2017: Virus Research
https://www.readbyqxmd.com/read/28412244/a-central-role-for-cadherin-signaling-in-cancer
#10
REVIEW
Antonis Kourtidis, Ruifeng Lu, Lindy J Pence, Panos Z Anastasiadis
Cadherins are homophilic adhesion molecules with important functions in cell-cell adhesion, tissue morphogenesis, and cancer. In epithelial cells, E-cadherin accumulates at areas of cell-cell contact, coalesces into macromolecular complexes to form the adherens junctions (AJs), and associates via accessory partners with a subcortical ring of actin to form the apical zonula adherens (ZA). As a master regulator of the epithelial phenotype, E-cadherin is essential for the overall maintenance and homeostasis of polarized epithelial monolayers...
April 12, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28410221/discovery-and-characterization-of-small-molecule-rac1-inhibitors
#11
Jamie L Arnst, Ashley L Hein, Margaret A Taylor, Nick Y Palermo, Jacob I Contreras, Yogesh A Sonawane, Andrew O Wahl, Michel M Ouellette, Amarnath Natarajan, Ying Yan
Aberrant activation of Rho GTPase Rac1 has been observed in various tumor types, including pancreatic cancer. Rac1 activates multiple signaling pathways that lead to uncontrolled proliferation, invasion and metastasis. Thus, inhibition of Rac1 activity is a viable therapeutic strategy for proliferative disorders such as cancer. Here we identified small molecule inhibitors that target the nucleotide-binding site of Rac1 through in silico screening. Follow up in vitro studies demonstrated that two compounds blocked active Rac1 from binding to its effector PAK1...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409572/-fret-based-biosensors-in-cell-migration-research
#12
Sławomir Lasota, Zbigniew Baster, Tomasz Witko, Eliza Zimoląg, Jolanta Sroka, Zenon Rajfur, Zbigniew Madeja
Cell migration is a complicated process, which is crucial for functioning of multicellular organisms. Multiple signalling pathways are deeply involved in the precise control of consecutive cell migration stages based on remodelling of the actin cytoskeleton. Small Rho GTPases (RhoA, Rac1 and Cdc42) as well as multiple protein and lipid kinases, calcium ions and mechanosensors are crucial components in this process. Exploration of those complicated correlations is possible with constant advancement of fluorescence microscopy...
2017: Postepy Biochemii
https://www.readbyqxmd.com/read/28409271/unique-presentation-of-cutis-laxa-with-leigh-like-syndrome-due-to-echs1-deficiency
#13
S Balasubramaniam, L G Riley, D Bratkovic, D Ketteridge, N Manton, M J Cowley, V Gayevskiy, T Roscioli, M Mohamed, T Gardeitchik, E Morava, J Christodoulou
Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM). Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade...
April 13, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28408954/rho-gtpases-in-ameloblast-differentiation
#14
REVIEW
Keishi Otsu, Hidemitsu Harada
During tooth development, ameloblasts differentiate from inner enamel epithelial cells to enamel-forming cells by modulating the signal pathways mediating epithelial-mesenchymal interaction and a cell-autonomous gene network. The differentiation process of epithelial cells is characterized by marked changes in their morphology and polarity, accompanied by dynamic cytoskeletal reorganization and changes in cell-cell and cell-matrix adhesion over time. Functional ameloblasts are tall, columnar, polarized cells that synthesize and secrete enamel-specific proteins...
May 2016: Japanese Dental Science Review
https://www.readbyqxmd.com/read/28404912/expression-of-rho-gtpases-family-in-melanoma-cells-and-its-influence-on-cytoskeleton-and-migration
#15
Si-Jian Wen, Wei Zhang, Na-Na Ni, Qiong Wu, Xiao-Po Wang, You-Kun Lin, Jian-Fang Sun
Rho GTPases family members influenced the filopodia, lamellipodia, stress fiber and adhesion plaque of melanoma cells through regulating cytoskeleton recombination. The role of Rho GTPases family in the migration and invasion of melanoma and its molecular mechanism were explored. The morphological difference between three types of melanoma cells (M14, A375 and MV3) and human melanocyte (MC) was observed by the Hoffman microscope. Cells were stained by phalloidin labeled by rhodamine. The differences between 4 types of cells in filopodia, lamellipodia, stress fiber and adhesion plaque (microfilament is the main constituent) were observed under the super-high resolution microscope...
February 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28394930/analysis-of-host-microrna-function-uncovers-a-role-for-mir-29b-2-5p-in-shigella-capture-by-filopodia
#16
Ushasree Sunkavalli, Carmen Aguilar, Ricardo Jorge Silva, Malvika Sharan, Ana Rita Cruz, Caroline Tawk, Claire Maudet, Miguel Mano, Ana Eulalio
MicroRNAs play an important role in the interplay between bacterial pathogens and host cells, participating as host defense mechanisms, as well as exploited by bacteria to subvert host cellular functions. Here, we show that microRNAs modulate infection by Shigella flexneri, a major causative agent of bacillary dysentery in humans. Specifically, we characterize the dual regulatory role of miR-29b-2-5p during infection, showing that this microRNA strongly favors Shigella infection by promoting both bacterial binding to host cells and intracellular replication...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28390160/the-role-of-small-gtpases-of-the-rho-rac-family-in-tgf-%C3%AE-induced-emt-and-cell-motility-in-cancer
#17
REVIEW
Hendrik Ungefroren, David Witte, Hendrik Lehnert
BACKGROUND: This article focusses on the role of Rho family GTPases and particularly Rac1 and Rac1b in TGF-β-induced epithelial-mesenchymal transition (EMT) and EMT-associated responses such as cell migration, invasion, and metastasis in cancer. RESULTS: EMT is considered a prerequisite for cells to adopt a motile and invasive phenotype and eventually become metastatic. A major regulator of EMT and metastasis in cancer is TGF-β and its specific functions on tumor cells are mediated besides Smad proteins and mitogen-activated protein kinases (MAPKs) by small GTPases of the Rho/Rac1 family...
April 8, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28389580/mgcracgap-s-sxip-motif-tethers-centralspindlin-to-microtubule-plus-ends
#18
Elaina B Breznau, Megan Murt, T Lynne Blasius, Kristen J Verhey, Ann L Miller
Centralspindlin, a complex of the kinesin-6 MKLP1 and MgcRacGAP, is required for cytokinesis and cell-cell junctions. During anaphase, Centralspindlin accumulates at overlapping central spindle microtubules and directs contractile ring formation by recruiting the GEF Ect2 to the cell equator to activate RhoA. We found that MgcRacGAP localized to plus ends of equatorial astral microtubules during cytokinesis in Xenopus laevis embryos. How MgcRacGAP is stabilized at microtubule plus ends is unknown. We identified an SxIP motif in X...
April 7, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28389565/akt3-kinase-suppresses-pinocytosis-of-low-density-lipoprotein-by-macrophages-via-novel-wnk-sgk1-cdc42-pathway
#19
Liang Ding, Lifang Zhang, Michael Kim, Tatiana Byzova, Eugene Podrez
Fluid-phase pinocytosis of Low-density lipoprotein (LDL) by macrophages is regarded as a novel promising target to reduce macrophage cholesterol accumulation in atherosclerotic lesions. The mechanisms of regulation of fluid-phase pinocytosis in macrophages and specifically the role of Akt kinases are poorly understood. We have previously found that increased lipoprotein uptake via the receptor independent process in Akt3 kinase deficient macrophages contributes to increased atherosclerosis in Akt3-/- mice. The mechanism by which Akt3 deficiency promotes lipoprotein uptake in macrophages is unknown...
April 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28386255/familial-mediterranean-fever-recent-developments-in-pathogenesis-and-new-recommendations-for-management
#20
REVIEW
Seza Özen, Ezgi Deniz Batu, Selcan Demir
Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease (AID) affecting mainly the ethnic groups originating from Mediterranean basin. The disease is characterized by self-limited inflammatory attacks of fever and polyserositis along with elevated acute phase reactants. FMF is inherited autosomal recessively; however, a significant proportion of heterozygotes also express the phenotype. FMF is caused by mutations in the MEFV gene coding for pyrin, which is a component of inflammasome functioning in inflammatory response and production of interleukin-1β (IL-1β)...
2017: Frontiers in Immunology
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