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Rac1 RhoA

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https://www.readbyqxmd.com/read/29925821/rho-gtpases-in-intellectual-disability-from-genetics-to-therapeutic-opportunities
#1
REVIEW
Valentina Zamboni, Rebecca Jones, Alessandro Umbach, Alessandra Ammoni, Maria Passafaro, Emilio Hirsch, Giorgio R Merlo
Rho-class small GTPases are implicated in basic cellular processes at nearly all brain developmental steps, from neurogenesis and migration to axon guidance and synaptic plasticity. GTPases are key signal transducing enzymes that link extracellular cues to the neuronal responses required for the construction of neuronal networks, as well as for synaptic function and plasticity. Rho GTPases are highly regulated by a complex set of activating (GEFs) and inactivating (GAPs) partners, via protein:protein interactions (PPI)...
June 20, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29913074/rho-gtpases-and-their-downstream-effectors-in-megakaryocyte-biology
#2
Irina Pleines, Deya Cherpokova, Markus Bender
Megakaryocytes differentiate from hematopoietic stem cells in the bone marrow. The transition of megakaryocytes to platelets is a complex process. Thereby, megakaryocytes extend proplatelets into sinusoidal blood vessels, where the proplatelets undergo fission to release platelets. Defects in platelet production can lead to a low platelet count (thrombocytopenia) with increased bleeding risk. Rho GTPases comprise a family of small signaling G proteins that have been shown to be master regulators of the cytoskeleton controlling many aspects of intracellular processes...
June 18, 2018: Platelets
https://www.readbyqxmd.com/read/29867343/complement-c3-affects-rac1-activity-in-the-developing-brain
#3
Anna Gorelik, Tamar Sapir, Lihi Ben-Reuven, Orly Reiner
The complement system, which is part of the innate immune response system, has been recently shown to participate in multiple key processes in the developing brain. Here we aimed to elucidate downstream signaling responses linking complement C3, a key molecule of the pathway, to small GTPases, known to affect the cytoskeleton. The expression pattern of the activated small GTPase Rac1 resembled that of complement C3. C3-deficient mice exhibited reduced Rac1 and elevated RhoA activity in comparison with control mice...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29799302/platelet-rho-gtpase-regulation-in-physiology-and-disease
#4
Joseph E Aslan
Rho GTPases are master orchestrators of cytoskeletal dynamics and serve critical roles in platelet physiology to promote hemostasis or pathology in thrombotic, inflammatory and other disease states. Over the past 25 years, specific platelet cell biological outputs have been linked to the activities of Rho GTPases, including RhoA, Rac1, Cdc42, and RhoG in shape change and secretion as well as cytoskeletal assembly events underlying platelet aggregation and thrombus stability. Rho GTPases have also more recently been noted to serve more specialized roles in platelet function and to cooperate with one another in mediating essential platelet responses...
May 25, 2018: Platelets
https://www.readbyqxmd.com/read/29784011/extremely-low-frequency-electromagnetic-fields-promote-mesenchymal-stem-cell-migration-by-increasing-intracellular-ca-2-and-activating-the-fak-rho-gtpases-signaling-pathways-in-vitro
#5
Yingchi Zhang, Jiyuan Yan, Haoran Xu, Yong Yang, Wenkai Li, Hua Wu, Chaoxu Liu
BACKGROUND: The ability of mesenchymal stem cells (MSCs) to migrate to the desired tissues or lesions is crucial for stem cell-based regenerative medicine and tissue engineering. Optimal therapeutics for promoting MSC migration are expected to become an effective means for tissue regeneration. Electromagnetic fields (EMF), as a noninvasive therapy, can cause a lot of biological changes in MSCs. However, whether EMF can promote MSC migration has not yet been reported. METHODS: We evaluated the effects of EMF on cell migration in human bone marrow-derived MSCs...
May 21, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29777701/ropivacaine-inhibits-the-migration-of-esophageal-cancer-cells-via-sodium-channel-independent-but-prenylation-dependent-inhibition-of-rac1-jnk-paxillin-fak
#6
Yaqin Zhang, Xiaohong Peng, Qinghong Zheng
The direct anti-proliferative and pro-apoptotic effects of local anesthetics have been well documented in various cancers. However, whether local anesthetics affect cancer metastasis and their underlying molecular mechanisms are not well understood. In this work, we show that ropivacaine at the clinically relevant concentration significantly inhibits esophageal cancer cell migration. Interestingly, ropivacaine at the same concentration does not display inhibitory effects on esophageal cancer cell growth and survival...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29776664/rhod-localization-and-function-is-dependent-on-its-gtp-gdp-bound-state-and-unique-n-terminal-motif
#7
Magdalena Blom, Katarina Reis, Pontus Aspenström
The atypical Rho GTPase RhoD has previously been shown to have a major impact on the organization and function of the actin filament system. However, when first discovered, RhoD was found to regulate endosome trafficking and dynamics and we therefore sought to investigate this regulation in more detail. We found that exogenously expressed RhoD in human fibroblasts localized to vesicles and the plasma membrane and that the active GTP-bound conformation was required for the plasma membrane localization but not for vesicle localization...
May 16, 2018: European Journal of Cell Biology
https://www.readbyqxmd.com/read/29772566/the-epigenetic-factor-kdm2b-regulates-emt-and-small-gtpases-in-colon-tumor-cells
#8
Nefeli Zacharopoulou, Anna Tsapara, Galatea Kallergi, Evi Schmid, Saad Alkahtani, Saud Alarifi, Philip N Tsichlis, Sotirios C Kampranis, Christos Stournaras
BACKGROUND/AIMS: The epigenetic factor KDM2B is a histone demethylase expressed in various tumors. Recently, we have shown that KDM2B regulates actin cytoskeleton organization, small Rho GTPases signaling, cell-cell adhesion and migration of prostate tumor cells. In the present study, we addressed its role in regulating EMT and small GTPases expression in colon tumor cells. METHODS: We used RT-PCR for the transcriptional analysis of various genes, Western blotting for the assessment of protein expression and immunofluorescence microscopy for visualization of fluorescently labeled proteins...
May 14, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29765517/targeting-the-mevalonate-pathway-is-a-novel-therapeutic-approach-to-inhibit-oncogenic-foxm1-transcription-factor-in-human-hepatocellular-carcinoma
#9
Satoshi Ogura, Yuichi Yoshida, Tomohide Kurahashi, Mayumi Egawa, Kunimaro Furuta, Shinichi Kiso, Yoshihiro Kamada, Hayato Hikita, Hidetoshi Eguchi, Hisakazu Ogita, Yuichiro Doki, Masaki Mori, Tomohide Tatsumi, Tetsuo Takehara
Dysregulation of cell metabolism is a hallmark of cancer. The mevalonate pathway in lipid metabolism has been implicated as a potential target of cancer therapy for hepatocellular carcinoma (HCC). The role of the Forkhead Box M1 (FoxM1) transcription factor in HCC development has been well documented, however, its involvement in cancer metabolism of HCC has not been fully determined. Here, we hypothesized that FoxM1 is involved in the mevalonate pathway of cholesterol biosynthesis in HCC. Inhibition of the mevalonate pathway by statins, inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR), resulted in reduced expression of FoxM1 and increased cell death in human hepatoma cells...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29752492/novel-antidepressant-effects-of-paeonol-alleviate-neuronal-injury-with-concomitant-alterations-in-bdnf-rac1-and-rhoa-levels-in-chronic-unpredictable-mild-stress-rats
#10
Xiu-Ling Zhu, Jing-Jing Chen, Fei Han, Chuan Pan, Ting-Ting Zhuang, Ya-Fei Cai, Ya-Ping Lu
RATIONALE: Increasing evidence has suggested that major depressive disorder (MDD) is highly associated with brain-derived neurotrophic factor (BDNF) levels, dendrites atrophy, and loss of dendritic spines, especially in emotion-associated brain regions including the hippocampus. Paeonol is a kind of polyphenols natural product with a variety of therapeutic effects. Recent studies have reported its antidepressant effects. However, it is unclear what signaling pathways contribute to improve MDD...
May 12, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29700112/rhoa-rac1-and-cdc42-differentially-regulate-%C3%AE-sma-and-collagen-i-expression-in-mesenchymal-stem-cells
#11
Jianfeng Ge, Laurent Burnier, Maria Adamopoulou, Mei Qi Kwa, Matthias Schaks, Klemens Rottner, Cord Brakebusch
Mesenchymal stem cells (MSC) are suggested to be important progenitors of myofibroblasts in fibrosis. To understand the role of Rho GTPase signaling in TGFβ-induced myofibroblast differentiation of MSC, we generated a novel MSC line and its descendants lacking functional Rho GTPases and Rho GTPase signaling components. Unexpectedly, our data revealed that Rho GTPase signaling is required for TGFβ-induced expression of α-smooth muscle actin (αSMA) but not of collagen I α1 ( col1a1 ). Whereas loss of RhoA and Cdc42 reduced αSMA expression, ablation of the Rac1 gene had the opposite effect...
June 15, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29686359/direct-multiplex-imaging-and-optogenetics-of-rho-gtpases-enabled-by-near-infrared-fret
#12
Daria M Shcherbakova, Natasha Cox Cammer, Tsipora M Huisman, Vladislav V Verkhusha, Louis Hodgson
Direct visualization and light control of several cellular processes is a challenge, owing to the spectral overlap of available genetically encoded probes. Here we report the most red-shifted monomeric near-infrared (NIR) fluorescent protein, miRFP720, and the fully NIR Förster resonance energy transfer (FRET) pair miRFP670-miRFP720, which together enabled design of biosensors compatible with CFP-YFP imaging and blue-green optogenetic tools. We developed a NIR biosensor for Rac1 GTPase and demonstrated its use in multiplexed imaging and light control of Rho GTPase signaling pathways...
June 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/29684861/inhibition-of-gastric-cancer-by-local-anesthetic-bupivacaine-through-multiple-mechanisms-independent-of-sodium-channel-blockade
#13
Jiapeng Dan, Xiaodan Gong, Dezhan Li, Guanhua Zhu, Lishen Wang, Fang Li
BACKGROUND: Retrospective studies of patients undergoing cancer surgery suggest the use of local anesthesia may decrease tumor recurrence and improve survival. The mechanisms on the benefits of local anesthesia on cancer recurrence are complex and remain to be elucidated. METHODS: This study investigated the effects of bupivacaine on various cellular activities of gastric cancer using proliferation, migration, apoptosis assay. The underlying mechanism was analyzed focusing on mitochondrial functions and the activities of Rho family members...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29683214/piezo1-functions-as-a-potential-oncogene-by-promoting-cell-proliferation-and-migration-in-gastric-carcinogenesis
#14
Jinglin Zhang, Yuhang Zhou, Tingting Huang, Feng Wu, Liping Liu, Johnny S H Kwan, Alfred S L Cheng, Jun Yu, Ka Fai To, Wei Kang
Gastric cancer (GC) is one of the most common malignancies in Asian areas. PIEZO1 has been implied to regulate epithelial homeostasis to play an important role in physiological processes. It is also related to tumor initiation and progression. However, the role of PIEZO1 has not yet been explored in GC. The expression of PIEZO1 in GC cell lines and primary samples was determined by qRT-PCR and Western blot. The clinical correlation of PIEZO1 in GC was evaluated by immunohistochemistry on tissue microarray. The oncogenic role of PIEZO1 was demonstrated in gastric tumorigenesis through a series of functional assays, including cell proliferation, cell invasion, and flow cytometry analysis...
April 23, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29678956/local-actin-polymerization-during-endocytic-carrier-formation
#15
REVIEW
Claudia Hinze, Emmanuel Boucrot
Extracellular macromolecules, pathogens and cell surface proteins rely on endocytosis to enter cells. Key steps of endocytic carrier formation are cargo molecule selection, plasma membrane folding and detachment from the cell surface. While dedicated proteins mediate each step, the actin cytoskeleton contributes to all. However, its role can be indirect to the actual molecular events driving endocytosis. Here, we review our understanding of the molecular steps mediating local actin polymerization during the formation of endocytic carriers...
April 20, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29615071/mature-and-progenitor-endothelial-cells-perform-angiogenesis-also-under-protease-inhibition-the-amoeboid-angiogenesis
#16
Anastasia Chillà, Francesca Margheri, Alessio Biagioni, Mario Del Rosso, Gabriella Fibbi, Anna Laurenzana
BACKGROUND: Controlling vascular growth is a challenging aim for the inhibition of tumor growth and metastasis. The amoeboid and mesenchymal types of invasiveness are two modes of migration interchangeable in cancer cells: the Rac-dependent mesenchymal migration requires the activity of proteases; the Rho-ROCK-dependent amoeboid motility is protease-independent and has never been described in endothelial cells. METHODS: A cocktail of physiologic inhibitors (Ph-C) of serine-proteases, metallo-proteases and cysteine-proteases, mimicking the physiological environment that cells encounter during their migration within the angiogenesis sites was used to induce amoeboid style migration of Endothelial colony forming cells (ECFCs) and mature endothelial cells (ECs)...
April 3, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29606008/mulberry-polyphenol-extract-inhibits-fak-src-pi3k-complex-and-related-signaling-to-regulate-the-migration-in-a7r5-cells
#17
Meng-Hsun Yu, Tsung-Yuan Yang, Hsieh-Hsun Ho, Hui-Pei Huang, Kuei-Chuan Chan, Chau-Jong Wang
Atherosclerosis is characterized by the buildup of plaque inside arteries. Our recent studies demonstrated that polyphenolic natural products can reduce oxidative stress, inflammation, angiogenesis, hyperlipidemia, and hyperglycemia. A previous study also showed that mulberry water extract (MWE) can inhibit atherosclerosis and contains considerable amounts of polyphenols. Therefore, in the present study, we investigated whether mulberry polyphenol extract (MPE) containing high levels of polyphenolic compounds could affect vascular smooth muscle cell (VSMC; A7r5 cell) motility...
April 18, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29543440/multiplexed-real-time-nmr-gtpase-assay-for-simultaneous-monitoring-of-multiple-guanine-nucleotide-exchange-factor-activities-from-human-cancer-cells-and-organoids
#18
Teklab Gebregiworgis, Christopher B Marshall, Tadateru Nishikawa, Nikolina Radulovich, María-José Sandí, Zhenhao Fang, Robert Rottapel, Ming-Sound Tsao, Mitsuhiko Ikura
Small GTPases (sGTPases) are critical switch-like regulators that mediate several important cellular functions and are often mutated in human cancers. They are activated by guanine nucleotide exchange factors (GEFs), which specifically catalyze the exchange of GTP for GDP. GEFs coordinate signaling networks in normal cells, and are frequently deregulated in cancers. sGTPase signaling pathways are complex and interconnected; however, most GEF assays do not reveal such complexity. In this Communication, we describe the development of a unique real-time NMR-based multiplexed GEF assay that employs distinct isotopic labeling schemes for each sGTPase protein to enable simultaneous observation of six proteins of interest...
April 4, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29541069/rac1-wave2-and-cdc42-n-wasp-participation-in-actin-dependent-host-cell-invasion-by-extracellular-amastigotes-of-trypanosoma-cruzi
#19
Alexis Bonfim-Melo, Éden R Ferreira, Renato A Mortara
This study evaluated the participation of host cell Rho-family GTPases and their effector proteins in the actin-dependent invasion by Trypanosoma cruzi extracellular amastigotes (EAs). We observed that all proteins were recruited and colocalized with actin at EA invasion sites in live or fixed cells. EA internalization was inhibited in cells depleted in Rac1, N-WASP, and WAVE2. Time-lapse experiments with Rac1, N-WASP and WAVE2 depleted cells revealed that EA internalization kinetics is delayed even though no differences were observed in the proportion of EA-induced actin recruitment in these groups...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29534999/diverse-signalling-of-the-platelet-p2y-1-receptor-leads-to-a-dichotomy-in-platelet-function
#20
Richard T Amison, Shirin Jamshidi, Khondaker M Rahman, Clive P Page, Simon C Pitchford
Platelet P2Y1 receptor signalling via RhoGTPases is necessary for platelet-dependent leukocyte recruitment, where no platelet aggregation is observed. We investigated signalling cascades involved in distinct P2Y1 -dependent platelet activities in vitro, using specific inhibitors for phospholipase C (PLC) (U73122, to inhibit the canonical pathway), and RhoGTPases: Rac1 (NSC23766) and RhoA (ROCK inhibitor GSK429286). Human platelet rich plasma (for platelet aggregation) or isolated washed platelets (for chemotaxis assays) was treated with U73122, GSK429286 or NSC23766 prior to stimulation with adenosine diphosphate (ADP) or the P2Y1 specific agonist MRS2365...
May 15, 2018: European Journal of Pharmacology
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