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https://www.readbyqxmd.com/read/28648016/-mechanisms-of-cytoskeleton-and-pi3k%C3%AE-rhoa-in-fine-particulate-matter-deteriorating-phagocytosis-defect-of-alveolar-macrophage-in-mice-with-chronic-obstructive-pulmonary-disease
#1
Q Xia, S T Hu, X L Zeng, H R Bao, X J Liu
Objective: To explore the mechanism of cytoskeleton and PI3Kδ-RhoA in fine particulate matter deteriorating phagocytosis defect of alveolar macrophage (AM) in chronic obstructive pulmonary disease (COPD) mice. Methods: Forty mice were randomly divided into four groups: health control group, COPD group, health PM2.5 group, COPD PM2.5 group and with ten in each group. A mouse model of COPD was established by cigarette smoke exposure, and health PM2.5 group and COPD PM2.5 group mice were given PM2.5 (588 μg/m(3)) aerosol inhalation for 90 days...
June 27, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28646092/deletion-analysis-of-agd1-reveals-domains-crucial-for-its-plasma-membrane-recruitment-and-function-in-root-hair-polarity
#2
Cheol-Min Yoo, Satoshi Naramoto, J Alan Sparks, Bibi Rafeiza Khan, Jin Nakashima, Hiroo Fukuda, Elison B Blancaflor
AGD1, a plant ACAP-type ADP-ribosylation factor-GTPase activating protein (ARF-GAP), functions in specifying root hair polarity in Arabidopsis thaliana To better understand how AGD1 modulates root hair growth, we generated full length and domain-deleted AGD1-green fluorescent protein (GFP) constructs, and followed their localization during root hair development. AGD1-GFP localized to the cytoplasm and was recruited to specific regions of the root hair plasma membrane (PM). Distinct PM AGD1-GFP signal was first detected along the site of root hair bulge formation...
June 23, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28645896/nucleotide-dependent-farnesyl-switch-orchestrates-polymerization-and-membrane-binding-of-human-guanylate-binding-protein-1
#3
Sergii Shydlovskyi, Anke Y Zienert, Semra Ince, Christine Dovengerds, Annika Hohendahl, Julia M Dargazanli, Ailisa Blum, Saskia D Günther, Nikolay Kladt, Michael Stürzl, Astrid C Schauss, Miriam Kutsch, Aurélien Roux, Gerrit J K Praefcke, Christian Herrmann
Dynamin-like proteins (DLPs) mediate various membrane fusion and fission processes within the cell, which often require the polymerization of DLPs. An IFN-inducible family of DLPs, the guanylate-binding proteins (GBPs), is involved in antimicrobial and antiviral responses within the cell. Human guanylate-binding protein 1 (hGBP1), the founding member of GBPs, is also engaged in the regulation of cell adhesion and migration. Here, we show how the GTPase cycle of farnesylated hGBP1 (hGBP1F) regulates its self-assembly and membrane interaction...
June 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28644898/spatio-temporal-orientation-of-microtubules-controls-conical-cell-shape-in-arabidopsis-thaliana-petals
#4
Huibo Ren, Xie Dang, Xianzhi Cai, Peihang Yu, Yajun Li, Shanshan Zhang, Menghong Liu, Binqing Chen, Deshu Lin
The physiological functions of epidermal cells are largely determined by their diverse morphologies. Most flowering plants have special conical-shaped petal epidermal cells that are thought to influence light capture and reflectance, and provide pollinator grips, but the molecular mechanisms controlling conical cell shape remain largely unknown. Here, we developed a live-confocal imaging approach to quantify geometric parameters of conical cells in Arabidopsis thaliana (A.thaliana). Through genetic screens, we identified katanin (KTN1) mutants showing a phenotype of decreased tip sharpening of conical cells...
June 23, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28644721/small-gtpases-in-plant-biotic-interactions
#5
Claudio Rivero, Soledad Traubenik, María Eugenia Zanetti, Flavio Antonio Blanco
The superfamily of small monomeric GTPases originated in a common ancestor of eukaryotic multicellular organisms and, since then, it has evolved independently in each lineage to cope with the environmental challenges imposed by their different life styles. Members of the small GTPase family function in the control of vesicle trafficking, cytoskeleton rearrangements and signaling during crucial biological processes, such as cell growth and responses to environmental cues. In this review, we discuss the emerging roles of these small GTPases in the pathogenic and symbiotic interactions established by plants with microorganisms present in their nearest environment, in which membrane trafficking is crucial along the different steps of the interaction, from recognition and signal transduction to nutrient exchange...
June 23, 2017: Small GTPases
https://www.readbyqxmd.com/read/28644713/an-unstructured-loop-that-is-critical-for-interactions-of-the-stalk-domain-of-drp1-with-saturated-phosphatidic-acid
#6
Yoshihiro Adachi, Miho Iijima, Hiromi Sesaki
Dynamin-related protein 1 (Drp1) is a dynamin superfamily GTPase, which drives membrane constriction during mitochondrial division. To mediate mitochondrial division, Drp1 is recruited to the mitochondrial outer membrane and is assembled into the division machinery. We previously showed that Drp1 interacts with phosphatidic acid (PA) and saturated phospholipids in the mitochondrial membrane, and this interaction restrains Drp1 in initiating the constriction of mitochondria. Here, we show that the role of saturated acyl chains of phospholipids is independent of their contribution to the membrane curvature or lipid packing suggesting their direct interaction with Drp1...
June 23, 2017: Small GTPases
https://www.readbyqxmd.com/read/28644070/particulate-matter-disrupts-human-lung-endothelial-cell-barrier-integrity-via-rho-dependent-pathways
#7
Ting Wang, Yuka Shimizu, Xiaomin Wu, Gabriel T Kelly, Xiaoyan Xu, Lichun Wang, Zhongqing Qian, Yin Chen, Joe G N Garcia
Increased exposure to ambient particulate matter (PM) is associated with elevated morbidity and mortality in patients with cardiopulmonary diseases and cancer. We and others have shown that PM induces lung microvascular barrier dysfunction which potentially enhances the systemic toxicity of PM. However, the mechanisms by which PM disrupts vascular endothelial integrity remain incompletely explored. We hypothesize that PM induces endothelial cell (EC) cytoskeleton rearrangement via Rho GTPase-dependent pathways to facilitate vascular hyperpermeability...
June 23, 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28643773/a-cdc42-rhoa-regulatory-circuit-downstream-of-glycoprotein-ib-guides-transendothelial-platelet-biogenesis
#8
Sebastian Dütting, Frederique Gaits-Iacovoni, David Stegner, Michael Popp, Adrien Antkowiak, Judith M M van Eeuwijk, Paquita Nurden, Simon Stritt, Tobias Heib, Katja Aurbach, Oguzhan Angay, Deya Cherpokova, Niels Heinz, Ayesha A Baig, Maximilian G Gorelashvili, Frank Gerner, Katrin G Heinze, Jerry Ware, Georg Krohne, Zaverio M Ruggeri, Alan T Nurden, Harald Schulze, Ute Modlich, Irina Pleines, Cord Brakebusch, Bernhard Nieswandt
Blood platelets are produced by large bone marrow (BM) precursor cells, megakaryocytes (MKs), which extend cytoplasmic protrusions (proplatelets) into BM sinusoids. The molecular cues that control MK polarization towards sinusoids and limit transendothelial crossing to proplatelets remain unknown. Here, we show that the small GTPases Cdc42 and RhoA act as a regulatory circuit downstream of the MK-specific mechanoreceptor GPIb to coordinate polarized transendothelial platelet biogenesis. Functional deficiency of either GPIb or Cdc42 impairs transendothelial proplatelet formation...
June 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28642683/object-phobia-and-altered-rhoa-signaling-in-amygdala-of-mice-lacking-rich2
#9
Tasnuva Sarowar, Stefanie Grabrucker, Tobias M Boeckers, Andreas M Grabrucker
RICH2 knockout (RICH2 KO) mice exhibit neophobia in the novel object test. To gain further insight into their anxiety-related phenotype, we subjected these mice to additional behavioral tests to elucidate whether the behavioral abnormality in these mice is a consequence of reduced exploratory motivation, and whether the neophobia is linked specifically to objects or also present for other modalities. RICH2 KO mice engage in normal exploration in a novel environment, suggesting that the anxiety-related phenotype is not due to reduced exploratory drive...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28642549/focal-adhesion-kinase-regulates-hepatic-stellate-cell-activation-and-liver-fibrosis
#10
Xue-Ke Zhao, Lei Yu, Ming-Liang Cheng, Pulin Che, Yin-Ying Lu, Quan Zhang, Mao Mu, Hong Li, Li-Li Zhu, Juan-Juan Zhu, Meng Hu, Po Li, Yue-Dong Liang, Xin-Hua Luo, Yi-Ju Cheng, Zhi-Xiang Xu, Qiang Ding
Understanding the underlying molecular mechanisms of liver fibrosis is important to develop effective therapy. Herein, we show that focal-adhesion-kinse (FAK) plays a key role in promoting hepatic stellate cells (HSCs) activation in vitro and liver fibrosis progression in vivo. FAK activation is associated with increased expression of α-smooth muscle actin (α-SMA) and collagen in fibrotic live tissues. Transforming growth factor beta-1 (TGF-β1) induces FAK activation in a time and dose dependent manner. FAK activation precedes the α-SMA expression in HSCs...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642463/acute-loss-of-the-hepatic-endo-lysosomal-system-in-vivo-causes-compensatory-changes-in-iron-homeostasis
#11
Christoph Metzendorf, Anja Zeigerer, Sarah Seifert, Richard Sparla, Bahar Najafi, François Canonne-Hergaux, Marino Zerial, Martina U Muckenthaler
Liver cells communicate with the extracellular environment to take up nutrients via endocytosis. Iron uptake is essential for metabolic activities and cell homeostasis. Here, we investigated the role of the endocytic system for maintaining iron homeostasis. We specifically depleted the small GTPase Rab5 in the mouse liver, causing a transient loss of the entire endo-lysosomal system. Strikingly, endosome depletion led to a fast reduction of hepatic iron levels, which was preceded by an increased abundance of the iron exporter ferroportin...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642362/regulation-of-rhoa-by-stat3-coordinates-glial-scar-formation
#12
Francois Renault-Mihara, Masahiko Mukaino, Munehisa Shinozaki, Hiromi Kumamaru, Satoshi Kawase, Matthieu Baudoux, Toshiki Ishibashi, Soya Kawabata, Yuichiro Nishiyama, Keiko Sugai, Kaori Yasutake, Seiji Okada, Masaya Nakamura, Hideyuki Okano
Understanding how the transcription factor signal transducer and activator of transcription-3 (STAT3) controls glial scar formation may have important clinical implications. We show that astrocytic STAT3 is associated with greater amounts of secreted MMP2, a crucial protease in scar formation. Moreover, we report that STAT3 inhibits the small GTPase RhoA and thereby controls actomyosin tonus, adhesion turnover, and migration of reactive astrocytes, as well as corralling of leukocytes in vitro. The inhibition of RhoA by STAT3 involves ezrin, the phosphorylation of which is reduced in STAT3-CKO astrocytes...
June 22, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28641564/investigation-on-the-interaction-of-pseudomonas-syringae-effector-avrpto-with-atrabe1d-gtpase
#13
Xiaomin Hou, Yi Gao
The tomato bacterial speck is a worldwide disease. It is caused by the infection of pathogenic pseudomonas syringae pv. tomato which delivers the effector AvrPto into the host cells via the type III secretion system. AvrPto interacts Rab8 subfamily protein in the GTP-bound form and participates in the response to pathogen infection, but the pathogenic mechanism involved by Rab8 subfamily remains elusive. Here, we investigated on the interrelationship of AvrPto8-159 with Arabidopsis thaliana GTP-restricted Rab8 subfamily protein AtRabE1d13-185Q74L through some biophysical and biochemical methods...
June 21, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28641032/targeting-rho-gtpase-effector-p21-activated-kinase-4-pak4-suppresses-p-bad-microrna-drug-resistance-axis-leading-to-inhibition-of-pancreatic-ductal-adenocarcinoma-proliferation
#14
Ramzi M Mohammad, Yiwei Li, Irfana Muqbil, Amro Aboukameel, William Senapedis, Erkan Baloglu, Yosef Landesman, Philip A Philip, Asfar S Azmi
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and therapy resistant malignancy. Mutant K-Ras, found in >90% of refractory PDAC, acts as a molecular switch activating Rho GTPase signaling that in turn promotes a plethora of pro-survival molecules and oncogenic microRNAs. We investigated the impact of Rho GTPase effector protein p21 activated kinase 4 (PAK4) inhibition on pro-survival p-Bad and oncogenic miRNA signaling. We demonstrate that the dual NAMPT and PAK4 modulators (KPT-9274 and KPT-9307) inhibit PDAC cell proliferation through down-regulation of Bad phosphorylation and up-regulation tumor suppressive miRNAs (miR-145, let-7c, let-7d, miR-34c, miR320 and miR-100)...
June 22, 2017: Small GTPases
https://www.readbyqxmd.com/read/28638915/-optogenetic-activation-of-dorsal-hippocampal-astrocytic-rac1-blocks-the-learning-of-associative-memory
#15
Xiao-Mu Guo, Zhao-Hui Liao, Ye-Zheng Tao, Fei-Fei Wang, Lan Ma
Rac1 belongs to the family of Rho GTPases, and plays important roles in the brain function. It affects the cell migration and axon guidance via regulating the cytoskeleton and cellular morphology. However, the effect of its dynamic activation in regulating physiological function remains unclear. Recently, a photoactivatable analogue of Rac1 (PA-Rac1) has been developed, allowing the activation of Rac1 by the specific wavelength of light in living cells. Thus, we constructed recombinant adeno-associated virus (AAV) of PA-Rac1 and its light-insensitive mutant PA-Rac1-C450A under the control of the mouse glial fibrillary acidic protein (mGFAP) promoter to manipulate Rac1 activity in astrocytes by optical stimulation...
June 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28638371/the-anticancer-peptide-tat-rasgap317-326-exerts-broad-antimicrobial-activity
#16
Mathieu Heulot, Nicolas Jacquier, Sébastien Aeby, Didier Le Roy, Thierry Roger, Evgeniya Trofimenko, David Barras, Gilbert Greub, Christian Widmann
Antibiotic resistance has become a major health issue. Nosocomial infections and the prevalence of resistant pathogenic bacterial strains are rising steadily. Therefore, there is an urgent need to develop new classes of antibiotics effective on multi-resistant nosocomial pathogenic bacteria. We have previously shown that a cell-permeable peptide derived from the p120 Ras GTPase-activating protein (RasGAP), called TAT-RasGAP317-326, induces cancer cell death, inhibits metastatic progression, and sensitizes tumor cells to various anti-cancer treatments in vitro and in vivo...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28636943/opa1-isoforms-in-the-hierarchical-organization-of-mitochondrial-functions
#17
Valentina Del Dotto, Prashant Mishra, Sara Vidoni, Mario Fogazza, Alessandra Maresca, Leonardo Caporali, J Michael McCaffery, Martina Cappelletti, Enrico Baruffini, Guy Lenaers, David Chan, Michela Rugolo, Valerio Carelli, Claudia Zanna
OPA1 is a GTPase that controls mitochondrial fusion, cristae integrity, and mtDNA maintenance. In humans, eight isoforms are expressed as combinations of long and short forms, but it is unclear whether OPA1 functions are associated with specific isoforms and/or domains. To address this, we expressed each of the eight isoforms or different constructs of isoform 1 in Opa1(-/-) MEFs. We observed that any isoform could restore cristae structure, mtDNA abundance, and energetic efficiency independently of mitochondrial network morphology...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636424/fluid-shear-stress-regulates-hepg2-cell-migration-though-time-dependent-integrin-signaling-cascade
#18
Hongchi Yu, Yang Shen, Jingsi Jin, Yingying Zhang, Tang Feng, Xiaoheng Liu
Hepatocellular carcinoma (HCC) is a subtype of malignant liver cancer with poor prognosis and limited treatment options. It is noteworthy that mechanical forces in tumor microenvironment play a pivotal role in mediating the behaviors and functions of tumor cells. As an instrumental type of mechanical forces in vivo, fluid shear stress (FSS) has been reported having potent physiologic and pathologic effects on cancer progression. However, the time-dependent mechanochemical transduction in HCC induced by FSS remains unclear...
June 21, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28634349/synuclein-impairs-trafficking-and-signaling-of-bdnf-in-a-mouse-model-of-parkinson-s-disease
#19
Fang Fang, Wanlin Yang, Jazmin B Florio, Edward Rockenstein, Brian Spencer, Xavier M Orain, Stephanie X Dong, Huayan Li, Xuqiao Chen, Kijung Sung, Robert A Rissman, Eliezer Masliah, Jianqing Ding, Chengbiao Wu
Recent studies have demonstrated that hyperphosphorylation of tau protein plays a role in neuronal toxicities of α-synuclein (ASYN) in neurodegenerative disease such as familial Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease. Using a transgenic mouse model of Parkinson's disease (PD) that expresses GFP-ASYN driven by the PDGF-β promoter, we investigated how accumulation of ASYN impacted axonal function. We found that retrograde axonal trafficking of brain-derived neurotrophic factor (BDNF) in DIV7 cultures of E18 cortical neurons was markedly impaired at the embryonic stage, even though hyperphosphorylation of tau was not detectable in these neurons at this stage...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634209/genetic-evidence-that-%C3%AE-arrestins-are-dispensable-for-the-initiation-of-%C3%AE-2-adrenergic-receptor-signaling-to-erk
#20
Morgan O'Hayre, Kelsie Eichel, Silvia Avino, Xuefeng Zhao, Dana J Steffen, Xiaodong Feng, Kouki Kawakami, Junken Aoki, Karen Messer, Roger Sunahara, Asuka Inoue, Mark von Zastrow, J Silvio Gutkind
The β2-adrenergic receptor (β2AR) has provided a paradigm to elucidate how G protein-coupled receptors (GPCRs) control intracellular signaling, including the discovery that β-arrestins, which bind to ligand-activated GPCRs, are central for GPCR function. We used genome editing, conditional gene deletion, and small interfering RNAs (siRNAs) to determine the roles of β-arrestin 1 (β-arr1) and β-arr2 in β2AR internalization, trafficking, and signaling to ERK. We found that only β-arr2 was essential for β2AR internalization...
June 20, 2017: Science Signaling
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