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Rho GTPases

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https://www.readbyqxmd.com/read/28811522/the-lichen-secondary-metabolite-atranorin-suppresses-lung-cancer-cell-motility-and-tumorigenesis
#1
Rui Zhou, Yi Yang, So-Yeon Park, Thanh Thi Nguyen, Young-Woo Seo, Kyung Hwa Lee, Jae Hyuk Lee, Kyung Keun Kim, Jae-Seoun Hur, Hangun Kim
Lichens are symbiotic organisms that produce various secondary metabolites. Here, different lichen extracts were examined to identify secondary metabolites with anti-migratory activity against human lung cancer cells. Everniastrum vexans had the most potent inhibitory activity, and atranorin was identified as an active subcomponent of this extract. Atranorin suppressed β-catenin-mediated TOPFLASH activity by inhibiting the nuclear import of β-catenin and downregulating β-catenin/LEF and c-jun/AP-1 downstream target genes such as CD44, cyclin-D1 and c-myc...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807941/the-rac-gtpase-in-cancer-from-old-concepts-to-new-paradigms
#2
Marcelo G Kazanietz, María-José Caloca
Rho family GTPases are critical regulators of cellular functions that play important roles in cancer progression. Aberrant activity of Rho small G-proteins, particularly Rac1 and their regulators, is a hallmark of cancer, and contributes to the tumorigenic and metastatic phenotypes of cancer cells. This review examines the multiple mechanisms leading to Rac1 hyperactivation, particularly focusing on emerging paradigms that involve gain-of-function mutations in Rac and guanine nucleotide exchange factors (GEFs), defects in Rac1 degradation, and mislocalization of Rac signaling components...
August 14, 2017: Cancer Research
https://www.readbyqxmd.com/read/28804736/urokinase-type-plasminogen-activator-upa-and-its-receptor-upar-promote-neurorepair-in-the-ischemic-brain
#3
Paola Merino, Ariel Diaz, Manuel Yepes
Despite the fact that ischemic stroke has been considered a leading cause of mortality in the world, recent advances in our understanding of the pathophysiological mechanisms underlying the ischemic injury and the treatment of acute ischemic stroke patients have led to a sharp decrease in the number of stroke deaths. However, this decrease in stroke mortality has also led to an increase in the number of patients that survive the acute ischemic injury with different degrees of disability. Unfortunately, to this date we do not have an effective therapeutic strategy to promote neurological recovery in these growing population of stroke survivors...
2017: Receptors & Clinical Investigation
https://www.readbyqxmd.com/read/28803875/a-novel-plasma-membrane-anchored-protein-regulates-xylem-cell-wall-deposition-through-microtubule-dependent-lateral-inhibition-of-rho-gtpase-domains
#4
Yuki Sugiyama, Mayumi Wakazaki, Kiminori Toyooka, Hiroo Fukuda, Yoshihisa Oda
Spatial control of cell-wall deposition is essential for determining plant cell shape [1]. Rho-type GTPases, together with the cortical cytoskeleton, play central roles in regulating cell-wall patterning [2]. In metaxylem vessel cells, which are the major components of xylem tissues, active ROP11 Rho GTPases form oval plasma membrane domains that locally disrupt cortical microtubules, thereby directing the formation of oval pits in secondary cell walls [3-5]. However, the regulatory mechanism that determines the planar shape of active Rho of Plants (ROP) domains is still unknown...
August 7, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28799243/escherichia-coli-k1-utilises-host-macropinocytic-pathways-for-invasion-of-brain-microvascular-endothelial-cells
#5
Lip Nam Loh, Elizabeth M C McCarthy, Priyanka Narang, Naveed A Khan, Theresa H Ward
Eukaryotic cells utilise multiple endocytic pathways for specific uptake of ligands or molecules, and these pathways are commonly hijacked by pathogens to enable host cell invasion. Escherichia coli K1, a pathogenic bacterium that causes neonatal meningitis, invades the endothelium of the blood-brain barrier, but the entry route remains unclear. Here we demonstrate that the bacteria trigger an actin-mediated uptake route, stimulating fluid phase uptake, membrane ruffling and macropinocytosis. The route of uptake requires intact lipid rafts as shown by cholesterol depletion...
August 11, 2017: Traffic
https://www.readbyqxmd.com/read/28799234/arhgef10-knockout-inhibits-platelet-aggregation-and-protects-mice-from-thrombus-formation
#6
Dai-Hua Lu, Chun-Chieh Hsu, Shiu-Wen Huang, Huang-Ju Tu, Tur-Fu Huang, Houng-Chi Liou, Hsiao-Mei Liao, Chia-Hsiang Chen, Wen-Mei Fu, Susan Shur-Fen Gau
BACKGROUND: ARHGEF10, a member of Rho guanine nucleotide exchange factors (GEF) family, stimulates the Rho GTPases. Rho GTPases have been reported to regulate a variety of cellular behaviors such as cell polarity, cytoskeletal organization and gene transcription. ARHGEF10 SNPs are linked with the risk of ischemic stroke. However, the role of ARHGEF10 in platelet function remains unknown. OBJECTIVE: To examine the role of ARHGEF10 in platelet function. METHODS: ARHGEF10 knockout mice were generated...
August 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28798145/tnf-induces-neutrophil-adhesion-via-formin-dependent-cytoskeletal-reorganization-and-activation-of-%C3%AE-integrin-function
#7
Angélica Aparecida Antoniellis Silveira, Venina Marcela Dominical, Camila Bononi Almeida, Hanan Chweih, Wilson Alves Ferreira, Cristina Pontes Vicente, Fabio Trindade Maranhão Costa, Claudio C Werneck, Fernando Ferreira Costa, Nicola Conran
Although essential for inflammatory responses, leukocyte recruitment to blood vessel walls in response to inflammatory stimuli, such as TNF-α, can contribute to vascular occlusion in inflammatory diseases, including atherosclerosis. We aimed to further characterize the mechanisms by which TNF stimulates adhesive and morphologic alterations in neutrophils. Microfluidic and intravital assays confirmed the potent effect that TNF has on human and murine neutrophil adhesion and recruitment in vitro and in vivo, respectively...
August 10, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28796249/rho-inhibition-by-lovastatin-affects-apoptosis-and-dsb-repair-of-primary-human-lung-cells-in-vitro-and-lung-tissue-in-vivo-following-fractionated-irradiation
#8
Verena Ziegler, Christian Henninger, Ioannis Simiantonakis, Marcel Buchholzer, Mohammad Reza Ahmadian, Wilfried Budach, Gerhard Fritz
Thoracic radiotherapy causes damage of normal lung tissue, which limits the cumulative radiation dose and, hence, confines the anticancer efficacy of radiotherapy and impacts the quality of life of tumor patients. Ras-homologous (Rho) small GTPases regulate multiple stress responses and cell death. Therefore, we investigated whether pharmacological targeting of Rho signaling by the HMG-CoA-reductase inhibitor lovastatin influences ionizing radiation (IR)-induced toxicity in primary human lung fibroblasts, lung epithelial and lung microvascular endothelial cells in vitro and subchronic mouse lung tissue damage following hypo-fractionated irradiation (4x4 Gy)...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28791309/research-progress-on-mechanism-of-podocyte-depletion-in-diabetic-nephropathy
#9
REVIEW
Haoran Dai, Qingquan Liu, Baoli Liu
Diabetic nephropathy (DN) together with glomerular hyperfiltration has been implicated in the development of diabetic microangiopathy in the initial stage of diabetic diseases. Increased amounts of urinary protein in DN may be associated with functional and morphological alterations of podocyte, mainly including podocyte hypertrophy, epithelial-mesenchymal transdifferentiation (EMT), podocyte detachment, and podocyte apoptosis. Accumulating studies have revealed that disruption in multiple renal signaling pathways had been critical in the progression of these pathological damages, such as adenosine monophosphate-activated kinase signaling pathways (AMPK), wnt/β-catenin signaling pathways, endoplasmic reticulum stress-related signaling pathways, mammalian target of rapamycin (mTOR)/autophagy pathway, and Rho GTPases...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28775097/platelet-derived-growth-factor-receptor-alpha-pdgfr%C3%AE-and-ras-related-c3-botulinum-toxin-substrate-1-rac1-regulate-mechano-responsiveness-of-lung-fibroblasts
#10
Stephen E McGowan, Diann M McCoy
Platelet-derived growth factor (PDGF)-A, which only signals through PDGF-receptor-alpha (PDGFRα) is required for secondary alveolar septal formation. Although PDGFRα distinguishes mesenchymal progenitor cells during the saccular stage, PDGFRα-expressing alveolar cells persist through adulthood. PDGF-A sustains proliferation, limits apoptosis, and maintains alpha-smooth muscle actin (αSMA) containing alveolar cells, which congregate at the alveolar entry ring at postnatal day (P)12. PDGFRα-expressing, αSMA-containing, alveolar cells re-distribute in the elongating septum, suggesting that they migrate to the alveolar entry rings where mechanical tension is higher...
August 3, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28767310/disrupted-irf6-nme1-2-complexes-as-a-cause-of-cleft-lip-palate
#11
M T Parada-Sanchez, E Y Chu, L L Cox, S S Undurty, J M Standley, J C Murray, T C Cox
Mutations and common polymorphisms in interferon regulatory factor 6 ( IRF6) are associated with both syndromic and nonsyndromic forms of cleft lip/palate (CLP). To date, much of the focus on this transcription factor has been on identifying its direct targets and the gene regulatory network in which it operates. Notably, however, IRF6 is found predominantly in the cytoplasm, with its import into the nucleus tightly regulated like other members of the IRF family. To provide further insight into the role of IRF6 in the pathogenesis of CLP, we sought to identify direct IRF6 protein interactors using a combination of yeast 2-hybrid screens and co-immunoprecipitation assays...
August 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28754775/retraction-for-sorek-et-al-activation-status-coupled-transient-s-acylation-determines-membrane-partitioning-of-a-plant-rho-related-gtpase
#12
Nadav Sorek, Limor Poraty, Hasana Sternberg, Einat Bar, Efraim Lewinsohn, Shaul Yalovsky
No abstract text is available yet for this article.
August 15, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28754687/cells-lay-their-own-tracks-optogenetic-cdc42-activation-stimulates-fibronectin-deposition-supporting-directed-migration
#13
Seth P Zimmerman, Sreeja B Asokan, Brian Kuhlman, James E Bear
Rho GTPase family members are known regulators of directed migration and therefore play key roles in processes including development, immune response and cancer metastasis. However, their individual contributions to these processes are complex. Here, we regulate the activity of two family members, Rac and Cdc42, by optogenetically recruiting specific GEF DH/PH domains to defined regions on the cell membrane. We find that the localized activation of both GTPases produce lamellipodia in cells plated on a fibronectin substrate...
July 28, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28751650/rhoa-phosphorylation-mediated-by-rho-rhoa-associated-kinase-pathway-improves-the-anti-freezing-potentiality-of-murine-hatched-and-diapaused-blastocysts
#14
Meichao Gu, Hemin Ni, Xihui Sheng, Alfredo Pauciullo, Yunhai Liu, Yong Guo
Embryonic cryopreservation has a relatively low survival rate because of cytoskeletal damage. However, molecular anti-freezing mechanisms have been largely unexplored. This study investigated the significance of RhoA, involved in embryonic development, and the Rho/RhoA-associated kinase (ROCK) signalling pathway in cryopreservation. The anti-freezing mechanism in murine dormant embryos, compared with normal blastocysts, was assessed by combining molecular, physiological and pharmacological approaches. Real-time PCR and western blotting experiments showed high RhoA expression in cryo-dormant and dormant embryos...
July 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747344/the-small-rho-gtpase-tc10-modulates-b-cell-immune-responses
#15
Marianne Burbage, Selina J Keppler, Beatriz Montaner, Pieta K Mattila, Facundo D Batista
Rho family GTPases regulate diverse cellular events, such as cell motility, polarity, and vesicle traffic. Although a wealth of data exists on the canonical Rho GTPases RhoA, Rac1, and Cdc42, several other family members remain poorly studied. In B cells, we recently demonstrated a critical role for Cdc42 in plasma cell differentiation. In this study, we focus on a close homolog of Cdc42, TC10 (also known as RhoQ), and investigate its physiological role in B cells. By generating a TC10-deficient mouse model, we show that despite reduced total B cell numbers, B cell development in these mice occurs normally through distinct developmental stages...
July 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28747072/regulation-of-staphylococcus-aureus-infection-of-macrophages-by-cd44-reactive-oxygen-species-and-acid-sphingomyelinase
#16
Cao Li, Yuqing Wu, Veronique Orian-Rousseau, Yang Zhang, Erich Gulbins, Heike Grassme
AIMS: Staphylococcus aureus plays an important role in sepsis, pneumonia, and wound infections. Acid sphingomyelinase (Asm)-deficient mice are highly susceptible to pulmonary S. aureus infections. Here, we investigated the role of CD44 as a molecule that mediates important aspects of the infection of macrophages with S. aureus. RESULTS: We showed that CD44 activation by S. aureus stimulated Asm via the formation of reactive oxygen species (ROS), resulting in ceramide release, clustering of CD44 in ceramide-enriched membrane platforms, CD44/Asm-dependent activation of Rho family GTPases, translocation of phospho-ezrin/radixin/moesin to the plasma-membrane, and a rapid rearrangement of the actin cytoskeleton with cortical actin polymerization...
July 26, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28742002/cdc42-activation-state-affects-its-localization-and-protein-levels-in-fission-yeast
#17
Miguel Estravís, Sergio Antonio Rincón, Elvira Portales, Pilar Pérez, Beatriz Santos
Rho GTPases control polarized cell growth and are well-known regulators of exocytic and endocytic processes. Cdc42 is an essential GTPase, conserved from yeast to humans, that is critical for cell polarization. Cdc42 is negatively regulated by the GTPase-activating proteins (GAPs) and the GDP dissociation inhibitors (GDIs), and positively regulated by guanine nucleotide exchange factors (GEFs). Cdc42 GTPase can be found in a GTP- or GDP-bound state, which determines the ability to bind downstream effector proteins and activate signalling pathways...
July 26, 2017: Microbiology
https://www.readbyqxmd.com/read/28739254/functional-analysis-of-the-promoters-of-the-small-gtpases-rhoa-and-rhob-in-embryonic-stem-cells
#18
Eirini Nomikou, Christos Stournaras, Dimitris Kardassis
Small GTPases of the Rho subfamily have been implicated in many physiological and pathological processes in various cell types including embryonic stem cells (ESCs). In the present study we performed a functional analysis of the promoters of the RhoA and the RhoB genes in order to identify regulatory elements that are important for their transcriptional control in ESCs. We show that RhoA mRNA levels of were significantly higher compared with the RhoB mRNA levels in ESCs as well in various cancer cell lines and this difference could be accounted for by differences in the activities of the corresponding promoters...
July 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28729673/distinct-functional-relevance-of-dynamic-gtpase-cysteine-methylation-in-fission-yeast
#19
Alejandro Franco, Teresa Soto, Rebeca Martín-García, Marisa Madrid, Beatriz Vázquez-Marín, Jero Vicente-Soler, Pedro M Coll, Mariano Gacto, Pilar Pérez, José Cansado
The final step in post-translational processing of Ras and Rho GTPases involves methylation of the prenylated cysteine residue by an isoprenylcysteine-O-carboxyl methyltransferase (ICMT). ICMT activity is essential for cell growth and development in higher eukaryotes, and inhibition of GTPase methylation has become an attractive target in cancer therapy to inactivate prenylated oncoproteins. However, the specificity and dynamics of the GTPase methylation process remain to be fully clarified. Notably, cells lacking Mam4, the ICMT ortholog in the fission yeast Schizosaccharomyces pombe, are viable...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724429/the-noncoding-rna-hoxd-as1-is-a-critical-regulator-of-the-metastasis-and-apoptosis-phenotype-in-human-hepatocellular-carcinoma
#20
Shan Lu, Jiansheng Zhou, Yimin Sun, Nan Li, Mingyong Miao, Binghua Jiao, Huan Chen
BACKGROUND: Despite accumulating evidence that long noncoding RNAs (lncRNAs) are associated with cancer development in multiple types of cancer, the biological roles of many lncRNAs in human hepatocellular carcinoma (HCC) metastasis have not been well characterized. METHODS: A lncRNA+ mRNA human gene expression microarray analysis was used to identify differentially expressed lncRNAs in metastatic HCC tissues compared to non-metastatic tissue. RESULTS: We observed remarkable overexpression of HOXD-AS1 in metastatic cancer tissues...
July 19, 2017: Molecular Cancer
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