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https://www.readbyqxmd.com/read/29678956/local-actin-polymerization-during-endocytic-carrier-formation
#1
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
#2
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
#3
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 2, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29543440/multiplexed-real-time-nmr-gtpase-assay-for-simultaneous-monitoring-of-multiple-gef-activities-from-human-cancer-cells-and-organoids
#4
Teklab Gebregiworgis, Christopher Boyd Marshall, Tadateru Nishikawa, Nikolina Radulovich, María-José Sandi, 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...
March 15, 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
#5
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-signaling-of-the-platelet-p2y-1-receptor-leads-to-a-dichotomy-in-platelet-function
#6
Richard T Amison, Shirin Jamshidi, Khondaker M Rahman, Clive P Page, Simon C Pitchford
Platelet P2Y1 receptor signaling via RhoGTPases is necessary for platelet-dependent leukocyte recruitment, where no platelet aggregation is observed. We investigated signaling 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...
March 10, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29532532/induction-of-keratinocyte-migration-by-eca-233-is-mediated-through-fak-akt-erk-and-p38-mapk-signaling
#7
Sawana Singkhorn, Mayuree H Tantisira, Supita Tanasawet, Pilaiwanwadee Hutamekalin, Tulaporn Wongtawatchai, Wanida Sukketsiri
Centella asiatica is widely considered the most important medicinal plant for treating and relieving skin diseases. Recently developed standardized extract of Centella asiatica ECa 233 has demonstrated positive effects on wound healing of incision and burn wound in rats. However, knowledge associated with wound healing mechanism of ECa 233 was scare. Therefore, this study aimed to investigate the effect and underlying molecular mechanisms of ECa 233 on the migration of a human keratinocyte cell line (HaCaT) using scratch wound healing assay...
March 13, 2018: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29492190/targeting-ovarian-cancer-and-endothelium-with-an-allosteric-ptp4a3-phosphatase-inhibitor
#8
Kelley E McQueeney, Joseph M Salamoun, James C Burnett, Nektarios Barabutis, Paula Pekic, Sophie L Lewandowski, Danielle C Llaneza, Robert Cornelison, Yunpeng Bai, Zhong-Yin Zhang, John D Catravas, Charles N Landen, Peter Wipf, John S Lazo, Elizabeth R Sharlow
Overexpression of protein tyrosine phosphatase PTP4A oncoproteins is common in many human cancers and is associated with poor patient prognosis and survival. We observed elevated levels of PTP4A3 phosphatase in 79% of human ovarian tumor samples, with significant overexpression in tumor endothelium and pericytes. Furthermore, PTP4A phosphatases appear to regulate several key malignant processes, such as invasion, migration, and angiogenesis, suggesting a pivotal regulatory role in cancer and endothelial signaling pathways...
February 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29491429/simulated-microgravity-inhibits-cell-focal-adhesions-leading-to-reduced-melanoma-cell-proliferation-and-metastasis-via-fak-rhoa-regulated-mtorc1-and-ampk-pathways
#9
Xin Tan, Aizhang Xu, Tuo Zhao, Qin Zhao, Jun Zhang, Cuihong Fan, Yulin Deng, Andrew Freywald, Harald Genth, Jim Xiang
Simulated microgravity (SMG) was reported to affect tumor cell proliferation and metastasis. However, the underlying mechanism is elusive. In this study, we demonstrate that clinostat-modelled SMG reduces BL6-10 melanoma cell proliferation, adhesion and invasiveness in vitro and decreases tumor lung metastasis in vivo. It down-regulates metastasis-related integrin α6β4, MMP9 and Met72 molecules. SMG significantly reduces formation of focal adhesions and activation of focal adhesion kinase (FAK) and Rho family proteins (RhoA, Rac1 and Cdc42) and of mTORC1 kinase, but activates AMPK and ULK1 kinases...
February 28, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29489426/an-explanation-for-how-fgfs-predict-species-specific-tooth-cusp-patterns
#10
L Li, Q Tang, H-J E Kwon, Z Wu, E-J Kim, H-S Jung
Species-specific cusp patterns result from the iterative formation of enamel knots, the epithelial signaling centers, at the future cusp positions. The expressions of fibroblast growth factors (FGFs), especially Fgf4, in the secondary enamel knots in the areas of the future cusp tips are generally used to manifest the appearance of species-specific tooth shapes. However, the mechanism underlying the predictive role of FGFs in species-specific cusp patterns remains obscure. Here, we demonstrated that gerbils, which have a lophodont pattern, exhibit a striped expression pattern of Fgf4, whereas mice, which have a bunodont pattern, have a spotted expression pattern, and these observations verify the predictive role of Fgf4 in species-specific cusp patterns...
February 1, 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29481523/flavonoids-extracted-from-leaves-of-diospyros-kaki-regulates-rhoa-activity-to-rescue-synapse-loss-and-reverse-memory-impairment-in-app-ps1-mice
#11
Yu-Ying Shang, Ying-Juan Ma, Lei Zhang, Li-Juan Wang, Xiao-Fan Wu, Xue-Ping Liu
Synapse dysfunction is an early hallmark of Alzheimer's disease (AD), and was considered to be closely related to memory loss. The molecular mechanisms that trigger synapse loss and dysfunction remain poorly understood. Increasing evidence shows a link between Rho GTPases and synapse plasticity. Rho GTPases play a role in controlling synapse function by regulating actin cytoskeleton and dendritic spines. Observations have suggested that phytochemicals, such as flavonoids, alleviate cognition impairment in AD...
February 23, 2018: Neuroreport
https://www.readbyqxmd.com/read/29454618/natural-small-molecule-bigelovin-suppresses-orthotopic-colorectal-tumor-growth-and-inhibits-colorectal-cancer-metastasis-via-il6-stat3-pathway
#12
Mingyue Li, Grace Gar-Lee Yue, Li-Hua Song, Mao-Bo Huang, Julia Kin-Ming Lee, Stephen Kwok-Wing Tsui, Kwok-Pui Fung, Ning-Hua Tan, Clara Bik-San Lau
Bigelovin, a sesquiterpene lactone, has been demonstrated to induce apoptosis, inhibit inflammation and angiogenesis in vitro, but its potential anti-metastatic activity remains unclear. In the present study, two colon cancer mouse models, orthotopic tumor allografts and experimental metastatic models were utilized to investigate the progression and metastatic spread of colorectal cancer after bigelovin treatments. Results showed that bigelovin (intravenous injection; 0.3-3 mg/kg) significantly suppressed tumor growth and inhibited liver/lung metastasis with modulation of tumor microenvironment (e...
February 15, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29440144/spon2-promotes-m1-like-macrophage-recruitment-and-inhibits-hepatocellular-carcinoma-metastasis-by-distinct-integrin-rho-gtpase-hippo-pathways
#13
Yan-Li Zhang, Qing Li, Xiao-Mei Yang, Fang Fang, Jun Li, Ya-Hui Wang, Qin Yang, Lei Zhu, Hui-Zhen Nie, Xue-Li Zhang, Ming-Xuan Feng, Shu-Heng Jiang, Guang-Ang Tian, Li-Peng Hu, Ho-Young Lee, Su-Jae Lee, Qiang Xia, Zhi-Gang Zhang
Tumor-associated macrophages (TAM) represent key regulators of the complex interplay between cancer and the immune microenvironment. Matricellular protein SPON2 is essential for recruiting lymphocytes and initiating immune responses. Recent studies have shown that SPON2 has complicated roles in cell migration and tumor progression. Here we report that, in the tumor microenvironment of hepatocellular carcinoma (HCC), SPON2 not only promotes infiltration of M1-like macrophages but also inhibits tumor metastasis...
February 13, 2018: Cancer Research
https://www.readbyqxmd.com/read/29432898/acarbose-inhibits-the-proliferation-and-migration-of-vascular-smooth-muscle-cells-via-targeting-ras-signaling
#14
Meng-Hsun Yu, Ming-Cheng Lin, Chien-Ning Huang, Kuei-Chuan Chan, Chau-Jong Wang
Atherosclerosis involves the proliferation and migration of vascular smooth muscle cells (VSMCs). The migration of VSMCs from the media into the intima and their subsequent proliferation are important processes in neointima formation in atherosclerosis and restenosis after percutaneous coronary interventions. Acarbose, an alpha-glucosidase inhibitor, has been demonstrated to not affect serum levels of glucose and decrease the progression of intima-media thickening in rabbits fed with a high cholesterol diet (HCD)...
February 9, 2018: Vascular Pharmacology
https://www.readbyqxmd.com/read/29424004/substrate-stiffness-regulated-migration-and-invasion-ability-of-adenoid-cystic-carcinoma-cells-via-rhoa-rock-pathway
#15
Dan Zhao, Qianshun Li, Mengting Liu, Wenjuan Ma, Tengfei Zhou, Changyue Xue, Xiaoxiao Cai
OBJECTIVES: Human salivary adenoid cystic carcinoma (SACC) is one of the most common malignant tumours of the salivary gland and has strong migratory and invasive ability, which often lead to poor prognosis and lower survival rate. Tumour tissue tends to stiffen during solid tumour progression. This study aimed to investigate the influence of various substrate stiffness on the migration and invasion of SACC. METHODS: Salivary adenoid cystic carcinoma cell line ACC2 cells were cultured on polydimethylsiloxane substrates (PDMS) with varying stiffness for investigating the effects of substrate stiffness on the activities of MMPs and TIMPs...
February 8, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29406266/systemic-or-forebrain-neuron-specific-deficiency-of-geranylgeranyltransferase-1-impairs-synaptic-plasticity-and-reduces-dendritic-spine-density
#16
David Hottman, Shaowu Cheng, Andrea Gram, Kyle LeBlanc, Li-Lian Yuan, Ling Li
Isoprenoids and prenylated proteins regulate a variety of cellular functions, including neurite growth and synaptic plasticity. Importantly, they are implicated in the pathogenesis of several diseases, including Alzheimer's disease (AD). Recently, we have shown that two protein prenyltransferases, farnesyltransferase (FT) and geranylgeranyltransferase-1 (GGT), have differential effects in a mouse model of AD. Haplodeficiency of either FT or GGT attenuates amyloid-β deposition and neuroinflammation but only reduction in FT rescues cognitive function...
February 2, 2018: Neuroscience
https://www.readbyqxmd.com/read/29377591/carboxylated-graphene-oxide-promoted-axonal-guidance-growth-by-activating-netrin-1-dcc-signaling-in-rat-primary-cultured-cortical-neurons
#17
Meili Liu, Zhengtai Jia, Xiongfu Xiao, Zhifa Zhang, Ping Li, Gang Zhou, Yubo Fan
Nanomaterials of graphene and its derivatives have been widely applied in recent years, but whose impacts on the neuronal guidance growth are still not reported. In the present study, graphene oxide (GO) and Carboxylated graphene oxide (GO-COOH) were used to investigate the potential effects on axonal guidance growth in the primary cultured cortical neurons. In addition,we characterized the structure and chemical composition of synthesized graphene oxide (GO) and carboxylated graphene oxide (GO-COOH) using Fourier transform infrared (FT-IR) spectrophotometer and Scanning Electron Microscope (SEM) assays and Raman analysis...
January 29, 2018: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29374533/circadian-control-of-p75-neurotrophin-receptor-leads-to-alternate-activation-of-nrf2-and-c-rel-to-reset-energy-metabolism-in-astrocytes-via-brain-derived-neurotrophic-factor
#18
REVIEW
Tetsuro Ishii, Eiji Warabi, Giovanni E Mann
Circadian clock genes regulate energy metabolism partly through neurotrophins in the body. The low affinity neurotrophin receptor p75NTR is a clock component directly regulated by the transcriptional factor Clock:Bmal1 complex. Brain-derived neurotrophic factor (BDNF) is expressed in the brain and plays a key role in coordinating metabolic interactions between neurons and astrocytes. BDNF transduces signals through TrkB and p75NTR receptors. This review highlights a novel molecular mechanism by which BDNF via circadian control of p75NTR leads to daily resetting of glucose and glycogen metabolism in brain astrocytes to accommodate their functional interaction with neurons...
January 24, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29373579/an-akap-lbc-rhoa-interaction-inhibitor-promotes-the-translocation-of-aquaporin-2-to-the-plasma-membrane-of-renal-collecting-duct-principal-cells
#19
Katharina Schrade, Jessica Tröger, Adeeb Eldahshan, Kerstin Zühlke, Kamal R Abdul Azeez, Jonathan M Elkins, Martin Neuenschwander, Andreas Oder, Mohamed Elkewedi, Sarah Jaksch, Karsten Andrae, Jinliang Li, Joao Fernandes, Paul Markus Müller, Stephan Grunwald, Stephen F Marino, Tanja Vukićević, Jenny Eichhorst, Burkhard Wiesner, Marcus Weber, Michael Kapiloff, Oliver Rocks, Oliver Daumke, Thomas Wieland, Stefan Knapp, Jens Peter von Kries, Enno Klussmann
Stimulation of renal collecting duct principal cells with antidiuretic hormone (arginine-vasopressin, AVP) results in inhibition of the small GTPase RhoA and the enrichment of the water channel aquaporin-2 (AQP2) in the plasma membrane. The membrane insertion facilitates water reabsorption from primary urine and fine-tuning of body water homeostasis. Rho guanine nucleotide exchange factors (GEFs) interact with RhoA, catalyze the exchange of GDP for GTP and thereby activate the GTPase. However, GEFs involved in the control of AQP2 in renal principal cells are unknown...
2018: PloS One
https://www.readbyqxmd.com/read/29370168/a-switch-in-the-mode-of-wnt-signaling-orchestrates-the-formation-of-germline-stem-cell-differentiation-niche-in-drosophila
#20
Maitreyi Upadhyay, Michael Kuna, Sara Tudor, Yesenia Martino Cortez, Prashanth Rangan
Germline stem cell (GSC) self-renewal and differentiation into gametes is regulated by both intrinsic factors in the germ line as well as extrinsic factors from the surrounding somatic niche. dWnt4, in the escort cells of the adult somatic niche promotes GSC differentiation using the canonical β-catenin-dependent transcriptional pathway to regulate escort cell survival, adhesion to the germ line and downregulation of self-renewal signaling. Here, we show that in addition to the β-catenin-dependent canonical pathway, dWnt4 also uses downstream components of the Wnt non-canonical pathway to promote escort cell function earlier in development...
January 2018: PLoS Genetics
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