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https://www.readbyqxmd.com/read/28923919/multiple-interactions-between-an-arf-gef-complex-and-charged-lipids-determine-activation-kinetics-on-the-membrane
#1
Deepti Karandur, Agata Nawrotek, John Kuriyan, Jacqueline Cherfils
Lipidated small GTPases and their regulators need to bind to membranes to propagate actions in the cell, but an integrated understanding of how the lipid bilayer exerts its effect has remained elusive. Here we focused on ADP ribosylation factor (Arf) GTPases, which orchestrate a variety of regulatory functions in lipid and membrane trafficking, and their activation by the guanine-nucleotide exchange factor (GEF) Brag2, which controls integrin endocytosis and cell adhesion and is impaired in cancer and developmental diseases...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28913759/biofuel-consumption-biodiversity-and-the-environmental-kuznets-curve-trivariate-analysis-in-a-panel-of-biofuel-consuming-countries
#2
Khalid Zaman
This study examined the relationship between biofuel consumption, forest biodiversity, and a set of national scale indicators of per capita income, foreign direct investment (FDI) inflows, trade openness, and population density with a panel data of 12 biofuels consuming countries for a period of 2000 to 2013. The study used Global Environmental Facility (GEF) biodiversity benefits index and forest biodiversity index in an environmental Kuznets curve (EKC) framework. The results confirmed an inverted U-shaped relationship between GEF biodiversity index and per capita income, while there is flat/no relationship between carbon emissions and economic growth, and between forest biodiversity and economic growth models...
September 14, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28912101/importance-of-the-rem-ras-exchange-domain-for-membrane-interactions-by-rasgrp3
#3
Agnes Czikora, Noemi Kedei, Heather Kalish, Peter M Blumberg
RasGRP comprises a family of guanine nucleotide exchange factors, regulating the dissociation of GDP from Ras GTPases to enhance the formation of the active GTP-bound form. RasGRP1 possesses REM (Ras exchange), GEF (catalytic), EF-hand, C1, SuPT (suppressor of PT), and PT (plasma membrane-targeting) domains, among which the C1 domain drives membrane localization in response to diacylglycerol or phorbol ester and the PT domain recognizes phosphoinositides. The homologous family member RasGRP3 shows less plasma membrane localization...
September 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28911825/paving-the-rho-in-cancer-metastasis-rho-gtpases-and-beyond
#4
REVIEW
Sepp Jansen, Reinoud Gosens, Thomas Wieland, Martina Schmidt
Malignant carcinomas are often characterized by metastasis, the movement of carcinoma cells from a primary site to colonize distant organs. For metastasis to occur, carcinoma cells first must adopt a pro-migratory phenotype and move through the surrounding stroma towards a blood or lymphatic vessel. Currently, there are very limited possibilities to target these processes therapeutically. The family of Rho GTPases is an ubiquitously expressed division of GTP-binding proteins involved in the regulation of cytoskeletal dynamics and intracellular signaling...
September 11, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28910410/the-function-of-drosophila-larval-class-iv-dendritic-arborization-sensory-neurons-in-the-larval-pupal-transition-is-separable-from-their-function-in-mechanical-nociception-responses
#5
Hannah E Brown, Trishna Desai, Allison J Murphy, Harshida Pancholi, Zachary W Schmidt, Hannah Swahn, Eric C Liebl
The sensory and physiological inputs which govern the larval-pupal transition in Drosophila, and the neuronal circuity that integrates them, are complex. Previous work from our laboratory identified a dosage-sensitive genetic interaction between the genes encoding the Rho-GEF Trio and the zinc-finger transcription factor Sequoia that interfered with the larval-pupal transition. Specifically, we reported heterozygous mutations in sequoia (seq) dominantly exacerbated the trio mutant phenotype, and this seq-enhanced trio mutant genotype blocked the transition of third instar larvae from foragers to wanderers, a requisite behavioral transition prior to pupation...
2017: PloS One
https://www.readbyqxmd.com/read/28894007/rabif-mss4-is-a-rab-stabilizing-holdase-chaperone-required-for-glut4-exocytosis
#6
Daniel R Gulbranson, Eric M Davis, Brittany A Demmitt, Yan Ouyang, Yihong Ye, Haijia Yu, Jingshi Shen
Rab GTPases are switched from their GDP-bound inactive conformation to a GTP-bound active state by guanine nucleotide exchange factors (GEFs). The first putative GEFs isolated for Rabs are RABIF (Rab-interacting factor)/MSS4 (mammalian suppressor of Sec4) and its yeast homolog DSS4 (dominant suppressor of Sec4). However, the biological function and molecular mechanism of these molecules remained unclear. In a genome-wide CRISPR genetic screen, we isolated RABIF as a positive regulator of exocytosis. Knockout of RABIF severely impaired insulin-stimulated GLUT4 exocytosis in adipocytes...
September 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28883040/genome-wide-sirna-screen-identifies-unc50-as-a-regulator-of-shiga-toxin-2-trafficking
#7
Andrey S Selyunin, Lakesla R Iles, Geoffrey Bartholomeusz, Somshuvra Mukhopadhyay
Shiga toxins 1 and 2 (STx1 and STx2) undergo retrograde trafficking to reach the cytosol. Early endosome-to-Golgi transport allows the toxins to evade degradation in lysosomes. Targeting this trafficking step has therapeutic promise, but the mechanism of trafficking for the more potent toxin STx2 is unclear. To identify host factors required for early endosome-to-Golgi trafficking of STx2, we performed a viability-based genome-wide siRNA screen in HeLa cells. 564, 535, and 196 genes were found to be required for toxicity induced by STx1 only, STx2 only, and both toxins, respectively...
September 7, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28882897/the-tiam1-guanine-nucleotide-exchange-factor-is-auto-inhibited-by-its-pleckstrin-homology-coiled-coil-extension-domain
#8
Zhen Xu, Lokesh Gakhar, Fletcher E Bain, Maria Spies, Ernesto J Fuentes
T-cell lymphoma invasion and metastasis 1 (Tiam1) is a Dbl-family guanine nucleotide exchange factor (GEF) that specifically activates the Rho-family GTPase Rac1 in response to upstream signals, thereby regulating cellular processes including cell adhesion and migration. Tiam1 contains multiple domains, including an N-terminal Pleckstrin homology coiled-coiled extension (PHn-CC-Ex) and catalytic Dbl-homology and C-terminal Pleckstrin homology (DH-PHc) domain. Previous studies indicate that larger fragments of Tiam1, such the region encompassing the N-terminal to C-terminal Pleckstrin homology domains (PHn-PHc) are auto-inhibited...
September 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28879181/regulation-of-the-sar1-gtpase-cycle-is-necessary-for-large-cargo-secretion-from-the-endoplasmic-reticulum
#9
REVIEW
Kota Saito, Miharu Maeda, Toshiaki Katada
Proteins synthesized within the endoplasmic reticulum (ER) are transported to the Golgi via coat protein complex II (COPII)-coated vesicles. The formation of COPII-coated vesicles is regulated by the GTPase cycle of Sar1. Activated Sar1 is recruited to ER membranes and forms a pre-budding complex with cargoes and the inner-coat complex. The outer-coat complex then stimulates Sar1 inactivation and completes vesicle formation. The mechanisms of forming transport carriers are well-conserved among species; however, in mammalian cells, several cargo molecules such as collagen, and chylomicrons are too large to be accommodated in conventional COPII-coated vesicles...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28876998/meiosis-specific-localization-of-the-exocytic-rab-ypt2-in-fission-yeast
#10
Kazuki Imada, Taro Nakamura
Fission yeast Ypt2, an orthologue of the mammalian small GTPase Rab8, is responsible for post-Golgi membrane trafficking. During meiosis, Ypt2 localizes at the spindle pole body (SPB), where it regulates de novo biogenesis of the spore plasma membrane. Recruitment of Ypt2 to the SPB is dependent on its meiosis-specific GDP/GTP exchange factor (GEF), the SPB-resident protein Spo13. Here we have examined the SPB recruitment of Ypt2 by Spo13. The GEF activity of Spo13 was required, but not essential for recruitment...
September 6, 2017: Small GTPases
https://www.readbyqxmd.com/read/28871449/arhgef39-promotes-gastric-cancer-cell-proliferation-and-migration-via-akt-signaling-pathway
#11
Haixiao Wang, Miaomiao Li, Xiaobao Tao, Yan Qian, Linfang Chen, Guoquan Tao
Dbl-family guanine nucleotide exchange factors (GEFs) can activate RhoGTPases by facilitating the exchange of GDP for GTP, the aberrant expression of which has been implicated in tumorigenicity and metastasis of human cancers. ARHGEF39, as a member of Dbl-family GEFs, was reported to be a potential oncogene in human hepatocellular carcinoma previously. However, the role of ARHGEF39 in gastric cancer (GC) remains unclear so far. In the current study, we demonstrated that ARHGEF39 expression was significantly upregulated in GC tissues compared with paired adjacent normal tissues by quantitative real-time PCR analysis...
September 4, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28860633/a-cdc42-centered-signaling-unit-is-a-dominant-positive-regulator-of-endothelial-integrity
#12
J Amado-Azevedo, N R Reinhard, J van Bezu, R X de Menezes, V W van Beusechem, G P van Nieuw Amerongen, V W M van Hinsbergh, P L Hordijk
Endothelial barrier function is carefully controlled to protect tissues from edema and damage inflicted by extravasated leukocytes. RhoGTPases, in conjunction with myriad regulatory proteins, exert both positive and negative effects on the endothelial barrier integrity. Precise knowledge about the relevant mechanisms is currently fragmented and we therefore performed a comprehensive analysis of endothelial barrier regulation by RhoGTPases and their regulators. Combining RNAi with electrical impedance measurements we quantified the relevance of 270 Rho-associated genes for endothelial barrier function...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28859988/cytoskeletal-remodeling-via-rho-gtpases-during-oxidative-and-thermal-stress-in-caenorhabditis-elegans
#13
Rahul Patel, Sindhu Sriramoji, Marena Marucci, Ibrahim Aziz, Sejal Shah, Federico Sesti
Biological systems are highly sensitive to changes in their environment. Indeed, the molecular basis of the environmental stress response suggests that the specialized stress responses share more commonalities than previously believed. Here, we used the nematode C. elegans to gain insight into the role of Rho signaling during two common environmental challenges, oxidative and thermal stress. In response to heat shock (HS), wild type (N2) worms demonstrated reduced viability which was rescued by genetic suppression of CDC42 and RHO-1...
August 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28858527/family-wide-analysis-of-the-inhibition-of-arf-guanine-nucleotide-exchange-factors-with-small-molecules-evidence-of-unique-inhibitory-profiles
#14
Sarah Benabdi, François Peurois, Agata Nawrotek, Jahnavi Chikireddy, Tatiana Cañeque, Takao Yamori, Isamu Shiina, Yoshimi Ohashi, Shingo Dan, Raphaël Rodriguez, Jacqueline Cherfils, Mahel Zeghouf
Arf GTPases and their guanine nucleotide exchange factors (ArfGEFs) are major regulators of membrane traffic and organelle structure in cells. They are associated with a variety of diseases and are thus attractive therapeutic targets for inhibition by small molecules. Several inhibitors of unrelated chemical structures have been discovered, which have shown their potential in dissecting molecular pathways and blocking disease-related functions. However, their specificity across the ArfGEF family has remained elusive...
September 13, 2017: Biochemistry
https://www.readbyqxmd.com/read/28857357/aspergillus-nidulans-baph-is-a-rab11-effector-that-connects-membranes-in-the-spitzenk%C3%A3-rper-with-basal-autophagy
#15
Mario Pinar, Miguel A Peñalva
Using affinity chromatography we identified the Aspergillus nidulans F-BAR-and-PH domain-containing protein BapH as a RabE(RAB11) effector. BapH localizes to the Spitzenkörper (SPK) in an F-actin- and Sec7-dependent manner, becoming cytosolic after inactivation of Trs120 in TRAPPII, the oligomeric GEF for RabE(RAB11) . Therefore RabE(RAB11) contributes to the recruitment of BapH to secretory vesicles in vivo. BapH has a close homologue, SlmA, which is related to yeast Slm1p/Slm2p, localizes to eisosomes and does not bind RabE(RAB11) ...
August 30, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28855378/adp-ribosylation-factor-like-4c-binding-to-filamin-a-modulates-filopodium-formation-and-cell-migration
#16
Tsai-Shin Chiang, Hsu-Feng Wu, Fang-Jen S Lee
Changes in cell morphology and the physical forces that occur during migration are generated by a dynamic filamentous actin cytoskeleton. The ADP-ribosylation factor-like 4C (Arl4C) small GTPase acts as a molecular switch to regulate morphological changes and cell migration, though the mechanism by which this occurs remains unclear. Here, we report that Arl4C functions with the actin regulator filamin-A (FLNa) to modulate filopodium formation and cell migration. We found that Arl4C interacted with FLNa in a GTP-dependent manner and that FLNa IgG repeat 22 is both required and sufficient for this interaction...
August 30, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28855187/inhibition-of-smooth-muscle-contraction-and-arf-6-activity-by-the-inhibitor-for-cytohesin-gefs-secinh3-in-the-human-prostate
#17
Annika Herlemann, Patrick Keller, Melanie Schott, Alexander Tamalunas, Anna Ciotkowska, Beata Rutz, Yiming Wang, Qingfeng Yu, Raphaela Waidelich, Frank Strittmatter, Christian G Stief, Christian Gratzke, Martin Hennenberg
Prostate smooth muscle contraction is critical for etiology and treatment of male lower urinary tract symptoms (LUTS), and is promoted by small monomeric GTPases (RhoA, Rac). GTPases may be activated by guanosine nucleotide exchange factors (GEFs). GEFs of the cytohesin family may indirectly activate Rac, or ADP ribosolyation factor (ARF) GTPases directly. Here we investigated the expression of cytohesin family GEFs, and effects of the cytohesin inhibitor secinH3 on smooth muscle contraction and GTPase activities in human prostate tissues...
August 30, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28854941/gefitinib-loaded-dspe-peg2000-nanomicelles-with-cd133-aptamers-target-lung-cancer-stem-cells
#18
Xiaolong Huang, Jingsong Huang, Dewen Leng, Shuo Yang, Qi Yao, Jin Sun, Jun Hu
BACKGROUND: Lung cancer stem cells (CSCs) are considered to be the seed of lung cancer, and CD133 is a marker of lung CSCs. Here, we developed gefitinib-loaded poly(ethylene glycol) 2000-distearoylphosphatidylethanolamine nanomicelles with CD133 aptamers (M-Gef-CD133) to eliminate CD133(+) lung CSCs. METHODS: M-Gef-CD133 was prepared using a lipid-film-based approach. The targeting and activity of M-Gef-CD133 towards lung CSCs were evaluated. RESULTS: M-Gef-CD133 were small (25 nm) and showed enhanced cytotoxic effect towards CD133(+) lung CSCs compared with non-targeted M-Gef and gefitinib...
August 30, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28853250/-rs-1-enhanced-the-efficiency-of-crispr-cas9-mediated-knock-in-of-human-lactoferrin
#19
Wenjun Zhou, Rihong Guo, Mingtian Deng, Feng Wang, Yanli Zhang
This study aims to knock out the goat β-lactoglobulin (BLG) gene using CRISPR-Cas9 system and knock in human lactoferrin (hLF) at the BLG locus, and further study the effect of RAD51 stimulatory compound (RS-1) on homologous recombination efficiency. First, we designed an sgRNA targeting the first exon of goat BLG gene and constructed a co-expression vector pCas9-sgBLG. This sgRNA vector was then transfected into goat ear fibroblasts (GEFs), and the target region was examined by T7EN1 assay and sequencing...
August 25, 2017: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://www.readbyqxmd.com/read/28842445/genetic-epilepsy-with-febrile-seizures-plus-refining-the-spectrum
#20
Yue-Hua Zhang, Rosemary Burgess, Jodie P Malone, Georgie C Glubb, Katherine L Helbig, Lata Vadlamudi, Sara Kivity, Zaid Afawi, Andrew Bleasel, Padraic Grattan-Smith, Bronwyn E Grinton, Susannah T Bellows, Danya F Vears, John A Damiano, Hadassa Goldberg-Stern, Amos D Korczyn, Leanne M Dibbens, Elizabeth K Ruzzo, Michael S Hildebrand, Samuel F Berkovic, Ingrid E Scheffer
OBJECTIVE: Following our original description of generalized epilepsy with febrile seizures plus (GEFS+) in 1997, we analyze the phenotypic spectrum in 409 affected individuals in 60 families (31 new families) and expand the GEFS+ spectrum. METHODS: We performed detailed electroclinical phenotyping on all available affected family members. Genetic analysis of known GEFS+ genes was carried out where possible. We compared our phenotypic and genetic data to those published in the literature over the last 19 years...
August 25, 2017: Neurology
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