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https://www.readbyqxmd.com/read/27910850/the-guanine-nucleotide-exchange-factor-net1-facilitates-the-specification-of-dorsal-cell-fates-in-zebrafish-embryos-by-promoting-maternal-%C3%AE-catenin-activation
#1
Shi Wei, Miaomiao Dai, Zhaoting Liu, Yuanqing Ma, Hanqiao Shang, Yu Cao, Qiang Wang
Wnt/β-catenin signaling is essential for the initiation of dorsal-ventral patterning during vertebrate embryogenesis. Maternal β-catenin accumulates in dorsal marginal nuclei during cleavage stages, but its critical target genes essential for dorsalization are silent until mid-blastula transition (MBT). Here, we find that zebrafish net1, a guanine nucleotide exchange factor, is specifically expressed in dorsal marginal blastomeres after MBT, and acts as a zygotic factor to promote the specification of dorsal cell fates...
December 2, 2016: Cell Research
https://www.readbyqxmd.com/read/27907191/trio-a-rho-family-gef-interacts-with-the-presynaptic-active-zone-proteins-piccolo-and-bassoon
#2
Ryan T Terry-Lorenzo, Viviana I Torres, Dhananjay Wagh, Jose Galaz, Selene K Swanson, Laurence Florens, Michael P Washburn, Clarissa L Waites, Eckart D Gundelfinger, Richard J Reimer, Craig C Garner
Synaptic vesicles (SVs) fuse with the plasma membrane at a precise location called the presynaptic active zone (AZ). This fusion is coordinated by proteins embedded within a cytoskeletal matrix assembled at the AZ (CAZ). In the present study, we have identified a novel binding partner for the CAZ proteins Piccolo and Bassoon. This interacting protein, Trio, is a member of the Dbl family of guanine nucleotide exchange factors (GEFs) known to regulate the dynamic assembly of actin and growth factor dependent axon guidance and synaptic growth...
2016: PloS One
https://www.readbyqxmd.com/read/27900608/interaction-of-epac-with-non-canonical-cyclic-nucleotides
#3
Holger Rehmann
Epac1 and Epac2 are cyclic nucleotide-binding (CNB) domain containing proteins, which were originally identified as cAMP-regulated guanine nucleotide exchange factors (GEFs) for the small G-protein Rap. Therefore, Epac proteins founded next to protein kinase A (PKA) and cyclic nucleotide-regulated ion channels the third group of cAMP-responsive proteins in higher organisms. Epac proteins are involved in the regulation of several physiological processes. In particular Epac1 mediates the regulation of molecular processes underlying cell adhesion and mobility...
November 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27887837/evaluating-the-influence-of-geo-environmental-factors-on-gully-erosion-in-a-semi-arid-region-of-iran-an-integrated-framework
#4
Omid Rahmati, Naser Tahmasebipour, Ali Haghizadeh, Hamid Reza Pourghasemi, Bakhtiar Feizizadeh
Despite the importance of soil erosion in sustainable development goals in arid and semi-arid areas, the study of the geo-environmental conditions and factors influencing gully erosion occurrence is rarely undertaken. As effort to this challenge, the main objective of this study is to apply an integrated approach of Geographic Object-Based Image Analysis (GEOBIA) together with high-spatial resolution imagery (SPOT-5) for detecting gully erosion features at the Kashkan-Poldokhtar watershed, Iran. We also aimed to apply a Conditional Probability (CP) model for establishing the spatial relationship between gullies and the Geo-Environmental Factors (GEFs)...
November 22, 2016: Science of the Total Environment
https://www.readbyqxmd.com/read/27876895/multiple-crosstalk-between-tor-and-the-cell-integrity-mapk-signaling-pathway-in-fission-yeast
#5
Marisa Madrid, Beatriz Vázquez-Marín, Alejandro Franco, Teresa Soto, Jero Vicente-Soler, Mariano Gacto, José Cansado
In eukaryotic cells, the highly conserved Target of Rapamycin (TOR) and the Mitogen Activated Protein Kinase (MAPK) signaling pathways elicit adaptive responses to extra- and intracellular conditions by regulating essential cellular functions. However, the nature of the functional relationships between both pathways is not fully understood. In the fission yeast Schizosaccharomyces pombe the cell integrity MAPK pathway (CIP) regulates morphogenesis, cell wall structure and ionic homeostasis. We show that the Rab GTPase Ryh1, a TORC2 complex activator, cross-activates the CIP and its core member, the MAPK Pmk1, by two distinct mechanisms...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27872253/gtpase-cross-talk-regulates-trappii-activation-of-rab11-homologues-during-vesicle-biogenesis
#6
Laura L Thomas, J Christopher Fromme
Rab guanosine triphosphatases (GTPases) control cellular trafficking pathways by regulating vesicle formation, transport, and tethering. Rab11 and its paralogs regulate multiple secretory and endocytic recycling pathways, yet the guanine nucleotide exchange factor (GEF) that activates Rab11 in most eukaryotic cells is unresolved. The large multisubunit transport protein particle (TRAPP) II complex has been proposed to act as a GEF for Rab11 based on genetic evidence, but conflicting biochemical experiments have created uncertainty regarding Rab11 activation...
November 21, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27871818/oxidatively-generated-base-modifications-in-dna-not-only-carcinogenic-risk-factor-but-also-regulatory-mark
#7
Marco Seifermann, Bernd Epe
The generation of DNA modifications in cells is in most cases accidental and associated with detrimental consequences such as increased mutation rates and an elevated risk of malignant transformation. Accordingly, repair enzymes involved in the removal of the modifications have primarily a protective function. Among the well-established exceptions of this rule are 5-methylcytosine and uracil, which are generated in DNA enzymatically under controlled conditions and fulfill important regulatory functions in DNA as epigenetic marks and in antibody diversification, respectively...
November 18, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27866705/epileptic-encephalopathy-caused-by-mutations-in-the-guanine-nucleotide-exchange-factor-dennd5a
#8
Chanshuai Han, Reem Alkhater, Tawfiq Froukh, Arakel G Minassian, Melissa Galati, Rui Han Liu, Maryam Fotouhi, Julia Sommerfeld, Ayman J Alfrook, Christian Marshall, Susan Walker, Peter Bauer, Stephen W Scherer, Olaf Riess, Rebecca Buchert, Berge A Minassian, Peter S McPherson
Epileptic encephalopathies are a catastrophic group of epilepsies characterized by refractory seizures and cognitive arrest, often resulting from abnormal brain development. Here, we have identified an epileptic encephalopathy additionally featuring cerebral calcifications and coarse facial features caused by recessive loss-of-function mutations in DENND5A. DENND5A contains a DENN domain, an evolutionarily ancient enzymatic module conferring guanine nucleotide exchange factor (GEF) activity to multiple proteins serving as GEFs for Rabs, which are key regulators of membrane trafficking...
December 1, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27864364/membrane-recruitment-of-the-non-receptor-protein-giv-girdin-g%C3%AE-interacting-vesicle-associated-protein-girdin-is-sufficient-for-activating-heterotrimeric-g-protein-signaling
#9
Kshitij Parag-Sharma, Anthony Leyme, Vincent DiGiacomo, Arthur Marivin, Stefan Broselid, Mikel Garcia-Marcos
GIV (aka Girdin) is a Guanine nucleotide Exchange Factor (GEF) that activates heterotrimeric G protein signaling downstream of RTKs and integrins, thereby serving as a platform for signaling cascade crosstalk. GIV is recruited to the cytoplasmic tail of receptors upon stimulation, but the mechanism of activation of its G protein regulatory function is not well understood. Here we used assays in humanized yeast models and G protein activity biosensors in mammalian cells to investigate the role of GIV subcellular compartmentalization in regulating its ability to promote G protein signaling...
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27854239/kshv-entry-and-trafficking-in-target-cells-hijacking-of-cell-signal-pathways-actin-and-membrane-dynamics
#10
REVIEW
Binod Kumar, Bala Chandran
Kaposi's sarcoma associated herpesvirus (KSHV) is etiologically associated with human endothelial cell hyperplastic Kaposi's sarcoma and B-cell primary effusion lymphoma. KSHV infection of adherent endothelial and fibroblast cells are used as in vitro models for infection and KSHV enters these cells by host membrane bleb and actin mediated macropinocytosis or clathrin endocytosis pathways, respectively. Infection in endothelial and fibroblast cells is initiated by the interactions between multiple viral envelope glycoproteins and cell surface associated heparan sulfate (HS), integrins (α3β1, αVβ3 and αVβ5), and EphA2 receptor tyrosine kinase (EphA2R)...
November 14, 2016: Viruses
https://www.readbyqxmd.com/read/27852895/ras-and-rab-interactor-1-controls-neuronal-plasticity-by-coordinating-dendritic-filopodial-motility-and-ampa-receptor-turnover
#11
Zsófia Szíber, Hanna Liliom, Carlos O Oueslati Morales, Attila Ignácz, Anikó Erika Rátkai, Kornelia Ellwanger, Gisela Link, Attila Szűcs, Angelika Hausser, Katalin Schlett
Ras and Rab interactor 1 (RIN1) is predominantly expressed in the nervous system. RIN1 knockout animals have deficits in latent inhibition and fear extinction in the amygdala, suggesting a critical role for RIN1 in preventing the persistence of unpleasant memories. At the molecular level, RIN1 signals through Rab5 GTPases that control endocytosis of cell-surface receptors and Abl non-receptor tyrosine kinases that participate in actin cytoskeleton remodelling.Here, we report that RIN1 controls the plasticity of cultured mouse hippocampal neurons...
November 16, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27849131/spatial-rho-regulation-molecular-mechanisms-controlling-the-gap-protein-dlc3
#12
Janina Hendrick, Monilola A Olayioye
The spatial regulation of cellular Rho signaling by GEF and GAP proteins and the molecular mechanisms controlling the Rho regulators themselves are still incompletely understood. We previously reported that the poorly characterized RhoGAP protein DLC3 localizes to cell-cell adhesions and Rab8-positive membrane tubules. However, it was unclear how DLC3 is targeted to these subcellular sites to execute its functions. In our recent work, protein partners of DLC3 were identified by mass spectrometry, identifying the basolateral polarity protein Scribble as a scaffold for DLC3 at cell-cell contacts...
November 16, 2016: Small GTPases
https://www.readbyqxmd.com/read/27835861/an-oncogenic-kras-transcription-program-activates-the-rhogef-arhgef2-to-mediate-transformed-phenotypes-in-pancreatic-cancer
#13
Oliver A Kent, María-José Sandí, Helen E Burston, Kevin R Brown, Robert Rottapel
Activating mutations of KRAS are nearly ubiquitous in pancreatic adenocarcinomas occurring in greater than 90% of cases. Cellular transformation by oncogenic RAS requires the RHO guanine exchange factor ARHGEF2 (also known as GEF-H1) for tumor growth and survival. Here, we find oncogenic KRAS activates ARHGEF2 through a minimal RAS responsive promoter. We have determined the endogenous ARHGEF2 promoter is positively regulated by the transcription factors ELK1, ETS1, SP1 and SP3 and negatively regulated by the RAS responsive element binding protein (RREB1)...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27833100/kinetics-of-recruitment-and-allosteric-activation-of-arhgef25-isoforms-by-the-heterotrimeric-g-protein-g%C3%AE-q
#14
Jakobus van Unen, Taofei Yin, Yi I Wu, Marieke Mastop, Theodorus W J Gadella, Joachim Goedhart
Rho GTPases are master regulators of the eukaryotic cytoskeleton. The activation of Rho GTPases is governed by Rho guanine nucleotide exchange factors (GEFs). Three RhoGEF isoforms are produced by the gene ARHGEF25; p63RhoGEF(580), GEFT and a recently discovered longer isoform of 619 amino acids (p63RhoGEF(619)). The subcellular distribution of p63RhoGEF(580) and p63RhoGEF(619) is strikingly different in unstimulated cells, p63RhoGEF(580) is located at the plasma membrane and p63RhoGEF(619) is confined to the cytoplasm...
November 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27832963/gotlr7-but-not-gotlr21-mediated-antiviral-immune-responses-against-low-pathogenic-h9n2-aiv-and-newcastle-disease-virus-infection
#15
Bing Yan, Jinyue Zhang, Wei Zhang, Mingshu Wang, Renyong Jia, Dekang Zhu, Mafeng Liu, Qiao Yang, Ying Wu, Kunfeng Sun, Xiaoyue Chen, Anchun Cheng, Shun Chen
Aquatic birds are considered the biological and genetic reservoirs of avian influenza virus and play a critical role in the transmission and dissemination of Newcastle Disease Virus (NDV). Both TLR7 and TLR21 are important for the host antiviral immune response. In an in vivo study, goTLR7, not goTLR21, was significantly up-regulated in the lungs of geese at 3 to 7 d after challenge with H9N2. And goOASL expression was induced in the bursa of fabricius, harderian glands and lungs. An increase in goRIG-I was detected in the lung and small intestine, whereas goPKR was increased in the lung but decreased in the thymus...
November 8, 2016: Immunology Letters
https://www.readbyqxmd.com/read/27830185/fhf1-fgf12-epileptic-encephalopathy
#16
Sameer Al-Mehmadi, Miranda Splitt, Venkateswaran Ramesh, Suzanne DeBrosse, Kimberly Dessoffy, Fan Xia, Yaping Yang, Jill A Rosenfeld, Patrick Cossette, Jacques L Michaud, Fadi F Hamdan, Philippe M Campeau, Berge A Minassian
Voltage-gated sodium channels (Navs) are mainstays of neuronal function, and mutations in the genes encoding CNS Navs (Nav1.1 [SCN1A], Nav1.2 [SCN2A], Nav1.3 [SCN3A], and Nav1.6 [SCN8A]) are causes of some of the most common and severe genetic epilepsies and epileptic encephalopathies (EE).(1) Fibroblast-growth-factor homologous factors (FHFs) compose a family of 4 proteins that interact with the C-terminal tails of Navs to modulate the channels' fast, and long-term, inactivations.(2)FHF2 mutation is a rare cause of generalized epilepsy with febrile seizures plus (GEFS+)...
December 2016: Neurology. Genetics
https://www.readbyqxmd.com/read/27816490/the-tumor-suppressor-cdx2-opposes-pro-metastatic-biomechanical-modifications-of-colon-cancer-cells-through-organization-of-the-actin-cytoskeleton
#17
Nadine Platet, Isabelle Hinkel, Ludovic Richert, Devadarssen Murdamoothoo, Ahlam Moufok-Sadoun, Marie Vanier, Philippe Lavalle, Christian Gaiddon, Dominique Vautier, Jean-Noel Freund, Isabelle Gross
The vast majority of cancer deaths are caused by the formation of metastases rather than the primary tumor itself. Despite this clinical importance, the molecular and cellular events that support the dissemination of cancer cells are not yet fully unraveled. We have previously shown that CDX2, a homeotic transcription factor essential for gut development, acts as a colon-specific tumor suppressor and opposes metastasis. Here, using a combination of biochemical, biophysical, and immunofluorescence techniques, we further investigated the mechanisms promoted by CDX2 that might antagonize tumor cell dissemination...
November 2, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27812215/paradoxical-sensitivity-to-an-integrated-stress-response-blocking-mutation-in-vanishing-white-matter-cells
#18
Yusuke Sekine, Alisa Zyryanova, Ana Crespillo-Casado, Niko Amin-Wetzel, Heather P Harding, David Ron
The eukaryotic translation initiation factor eIF2B promotes mRNA translation as a guanine nucleotide exchange factor (GEF) for translation initiation factor 2 (eIF2). Endoplasmic reticulum (ER) stress-mediated activation of the kinase PERK and the resultant phosphorylation of eIF2's alpha subunit (eIF2α) attenuates eIF2B GEF activity thereby inducing an integrated stress response (ISR) that defends against protein misfolding in the ER. Mutations in all five subunits of human eIF2B cause an inherited leukoencephalopathy with vanishing white matter (VWM), but the role of the ISR in its pathogenesis remains unclear...
2016: PloS One
https://www.readbyqxmd.com/read/27810516/is-fgf13-a-major-contributor-to-genetic-epilepsy-with-febrile-seizures-plus
#19
Kristin A Rigbye, Peter M van Hasselt, Rosemary Burgess, John A Damiano, Saul A Mullen, Slavé Petrovski, Ram S Puranam, Koen L I van Gassen, Jozef Gecz, Ingrid E Scheffer, James O McNamara, Samuel F Berkovic, Michael S Hildebrand
Mutation of fibroblast growth factor 13 (FGF13) has recently been implicated in genetic epilepsy with febrile seizures plus (GEFS+) in a single family segregating a balanced translocation with a breakpoint in this X chromosome gene, predicting a partial knockout involving 3 of 5 known FGF13 isoforms. Investigation of a mouse model of complete Fgf13 knock-out revealed increased susceptibility to hyperthermia-induced seizures and epilepsy. Here we investigated whether mutation of FGF13 would explain other cases of GEFS+ compatible with X-linked inheritance...
December 2016: Epilepsy Research
https://www.readbyqxmd.com/read/27799911/huperzine-a-provides-robust-and-sustained-protection-against-induced-seizures-in-scn1a-mutant-mice
#20
Jennifer C Wong, Stacey B B Dutton, Stephen D Collins, Steven Schachter, Andrew Escayg
De novo loss-of-function mutations in the voltage-gated sodium channel (VGSC) SCN1A (encoding Nav1.1) are the main cause of Dravet syndrome (DS), a catastrophic early-life encephalopathy associated with prolonged and recurrent early-life febrile seizures (FSs), refractory afebrile epilepsy, cognitive and behavioral deficits, and a 15-20% mortality rate. SCN1A mutations also lead to genetic epilepsy with febrile seizures plus (GEFS+), which is an inherited disorder characterized by early-life FSs and the development of a range of adult epilepsy subtypes...
2016: Frontiers in Pharmacology
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