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https://www.readbyqxmd.com/read/28096473/vimentin-intermediate-filaments-control-actin-stress-fiber-assembly-through-gef-h1-and-rhoa
#1
Yaming Jiu, Johan Peränen, Niccole Schaible, Fang Cheng, John E Eriksson, Ramaswamy Krishnan, Pekka Lappalainen
The actin and intermediate filament cytoskeleltons contribute to numerous cellular processes, including morphogenesis, cytokinesis, and migration. These two cytoskeletal systems associate with each other, but the underlying mechanisms are incompletely understood. Here,we show that inactivation of vimentin leads to increased actin stress fiber assembly and contractility, and consequent elevation of myosin light chain phosphorylation and stabilization of tropomyosin-4.2. The vimentin knockout phenotypes can be rescued by re-expression of wild-type vimentin, but not by the non-filamentous 'unit length form' vimentin, demonstrating that intact vimentin intermediate filaments are required to facilitate the effects on the actin cytoskeleton...
January 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28095644/xenopus-as-a-model-organism-to-study-heterotrimeric-g-protein-pathway-during-collective-cell-migration-of-neural-crest
#2
REVIEW
G Toro-Tapia, S Villaseca, J I Leal, A Beyer, J Fuentealba, M Torrejón
Collective cell migration is essential in many fundamental aspects of normal development, like morphogenesis, organ formation, wound healing and immune responses, as well as in the etiology of severe pathologies, like cancer metastasis. In spite of the huge amount of data accumulated on cell migration, such a complex process involves many molecular actors, some of which still remain to be functionally characterized. One of these signals is the heterotrimeric G-protein pathway that has been studied mainly in gastrulation movements...
January 17, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28087633/the-abl-pathway-bifurcates-to-balance-enabled-and-rac-signaling-in-axon-patterning-in-drosophila
#3
Ramakrishnan Kannan, Jeong-Kuen Song, Tatiana Karpova, Akanni Clarke, Madhuri Shivalkar, Benjamin Wang, Lyudmila Kotlyanskaya, Irina Kuzina, Qun Gu, Edward Giniger
The Abl tyrosine kinase signaling network controls cell migration, epithelial organization, axon patterning and other aspects of development. While individual components are known, the relationships among them remain mysterious. We now use FRET measurements of pathway activity, analysis of protein localization and genetic epistasis to dissect the structure of this network in Drosophila We find that the adaptor protein Disabled stimulates Abl kinase activity. Abl suppresses the actin regulatory factor Enabled, and we find that Abl also acts through the GEF Trio to stimulate the signaling activity of Rac GTPase: Abl gates the activity of the spectrin repeats of Trio, allowing them to relieve intramolecular repression of Trio GEF activity by the Trio N-terminal domain...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28070485/vagus-nerve-stimulation-for-genetic-epilepsy-with-febrile-seizures-plus-gefs-accompanying-seizures-with-impaired-consciousness
#4
Ryosuke Hanaya, Fajar H Niantiarno, Yumi Kashida, Hiroshi Hosoyama, Shinsuke Maruyama, Toshiaki Otsubo, Kazumi Tanaka, Atsushi Ishii, Shinichi Hirose, Kazunori Arita
Genetic epilepsy with febrile seizures plus (GEFS(+)) is characterized by childhood-onset epilepsy syndrome. It involves febrile seizures and a variety of afebrile epileptic seizure types within the same pedigree with autosomal-dominant inheritance. Approximately 10% of individuals with GEFS(+) harbor SCN1A, a gene mutation in one of the voltage-gated sodium channel subunits. Considerably less common are focal epilepsies including complex partial seizures. We report vagus nerve stimulation (VNS) in a 6-year-old girl with GEFS(+) who exhibited refractory generalized tonic-clonic seizures and complex partial seizures...
2017: Epilepsy & Behavior Case Reports
https://www.readbyqxmd.com/read/28069739/a-two-tiered-mechanism-enables-localized-cdc42-signaling-during-enterocyte-polarization
#5
Lucas J M Bruurs, Susan Zwakenberg, Mirjam C van der Net, Fried J Zwartkruis, Johannes L Bos
Signaling by the small GTPase Cdc42 governs a diverse set of cellular processes that contribute to tissue morphogenesis. Since these processes often require highly localized signaling, Cdc42 activity must be clustered in order to prevent ectopic signaling. During cell polarization, apical Cdc42 signaling directs the positioning of the nascent apical membrane. However, the molecular mechanisms that drive Cdc42 clustering during polarity establishment are largely unknown.Here we demonstrate that during cell polarization localized Cdc42 signaling is enabled via activity-dependent control of Cdc42 mobility...
January 9, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28065575/multiparametric-analysis-of-cell-shape-demonstrates-that-%C3%AE-pix-directly-couples-yap-activation-to-extracellular-matrix-adhesion
#6
Julia E Sero, Chris Bakal
Mechanical signals from the extracellular matrix (ECM) and cellular geometry regulate the nuclear translocation of transcriptional regulators such as Yes-associated protein (YAP). Elucidating how physical signals control the activity of mechanosensitive proteins poses a technical challenge, because perturbations that affect cell shape may also affect protein localization indirectly. Here, we present an approach that mitigates confounding effects of cell-shape changes, allowing us to identify direct regulators of YAP localization...
January 2, 2017: Cell Systems
https://www.readbyqxmd.com/read/28063497/pld-protein-protein-interactions-with-signaling-molecules-and-modulation-by-pa
#7
J Gomez-Cambronero, A J Morris, K M Henkels
We describe methods for studying phospholipase D (PLD) interactions with signaling proteins and modulation of these interactions by the PLD reaction product, phosphatidic acid (PA). PLD is fundamental to the physiological maintenance of cellular/intracellular membranes, protein trafficking, cytoskeletal dynamics, membrane remodeling, cell proliferation, meiotic division and sporulation. PA is an acidic phospholipid involved in the biosynthesis of many other lipids that affects the enzymatic activities of many different signaling proteins via protein-lipid interactions or as a substrate...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28060719/temporal-quantitative-phosphoproteomics-of-adp-stimulation-reveals-novel-central-nodes-in-platelet-activation-and-inhibition
#8
Florian Beck, Jörg Geiger, Stepan Gambaryan, Fiorella A Solari, Margherita Dell'Aica, Stefan Loroch, Nadine Mattheij, Igor Mindukshev, Oliver Pötz, Kerstin Jurk, Julia M Burkhart, Christian Fufezan, Johan W M Heemskerk, Ulrich Walter, René P Zahedi, Albert Sickmann
ADP enhances platelet activation by virtually any other stimulant to complete aggregation. It binds specifically to the G-protein coupled membrane receptors P2Y1 and P2Y12, stimulating intracellular signaling cascades leading to integrin αIIbβ3 activation, a process that is antagonized by endothelial prostacyclin. P2Y12 inhibitors are among the most successful anti-platelet drugs, however, show remarkable variability in efficacy. We reasoned whether a more detailed molecular understanding of ADP-induced protein phosphorylation could identify (i) critical hubs in platelet signaling towards aggregation, and (ii) novel molecular targets for anti-platelet treatment strategies...
November 9, 2016: Blood
https://www.readbyqxmd.com/read/28055292/molecular-control-of-rab-activity-by-gefs-gaps-and-gdi
#9
Matthias P Müller, Roger S Goody
Rab proteins are the major regulators of vesicular trafficking in eukaryotic cells. Their activity can be tightly controlled within cells: Regulated by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), they switch between an active GTP-bound state and an inactive GDP-bound state, interacting with downstream effector proteins only in the active state. Additionally, they can bind to membranes via C-terminal prenylated cysteine residues and they can be solubilized and shuttled between membranes by chaperone-like molecules called GDP dissociation inhibitors (GDIs)...
January 5, 2017: Small GTPases
https://www.readbyqxmd.com/read/28051187/architecture-and-mechanism-of-the-late-endosomal-rab7-like-ypt7-guanine-nucleotide-exchange-factor-complex-mon1-ccz1
#10
Stephan Kiontke, Lars Langemeyer, Anne Kuhlee, Saskia Schuback, Stefan Raunser, Christian Ungermann, Daniel Kümmel
The Mon1-Ccz1 complex (MC1) is the guanine nucleotide exchange factor (GEF) for the Rab GTPase Ypt7/Rab7 and is required for endosomal maturation and fusion at the vacuole/lysosome. Here we present the overall architecture of MC1 from Chaetomium thermophilum, and in combining biochemical studies and mutational analysis in yeast, we identify the domains required for catalytic activity, complex assembly and localization of MC1. The crystal structure of a catalytic MC1 core complex bound to Ypt7 provides mechanistic insight into its function...
January 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28036092/human-rho-guanine-nucleotide-exchange-factor-11-arhgef11-regulates-dendritic-morphogenesis
#11
Yutaka Mizuki, Manabu Takaki, Shinji Sakamoto, Sojiro Okamoto, Makiko Kishimoto, Yuko Okahisa, Masahiko Itoh, Norihito Yamada
Disturbances of synaptic connectivity during perinatal and adolescent periods have been hypothesized to be related to the pathophysiology of schizophrenia. Rho guanine nucleotide exchange factor 11 (ARHGEF11) is a specific guanine nucleotide exchange factors (GEF) for RhoA, which is a critical regulator of actin cytoskeleton dynamics and organization of dendritic spines and inhibitor of spine maintenance. ARHGEF11 variants are reported to be associated with a higher risk for the onset of schizophrenia in a Japanese population; however, how ARHGEF11 contributes to the pathogenesis of schizophrenia in dendritic spines is unknown...
December 29, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28029388/emerging-role-of-cdc42-specific-guanine-nucleotide-exchange-factors-as-regulators-of-membrane-trafficking-in-health-and-disease
#12
REVIEW
M V Egorov, R S Polishchuk
It is widely accepted that the Golgi complex operates as a main sorting station in the biosynthetic pathway. On the other hand, the Golgi complex harbors numerous signaling molecules that generate the platform for the coordination of the transduction of specific signals and of membrane transport events. A part of these processes, which require the complex integration of transport-, cytoskeleton- and polarity-associated mechanisms, is tightly regulated by molecular machineries comprising guanine nucleotide exchange factors (GEF) and their down-stream effectors, such as the small GTPase Cdc42...
October 19, 2016: Tissue & Cell
https://www.readbyqxmd.com/read/28028174/dock8-regulates-macrophage-migration-through-cdc42-activation-and-lrap35a-interaction
#13
Akira Shiraishi, Takehito Uruno, Fumiyuki Sanematsu, Miho Ushijima, Daiji Sakata, Toshiro Hara, Yoshinori Fukui
DOCK8 is an atypical guanine nucleotide exchange factor (GEF) for Cdc42, and its mutations cause combined immunodeficiency in humans. Accumulating evidence indicates that DOCK8 regulates the migration and activation of various subsets of leukocytes, yet its regulatory mechanism is poorly understood. We herein report that DOCK8-deficient macrophages exhibit a migration defect in a two-dimensional (2D) setting. Although DOCK8 deficiency in macrophages did not affect the global Cdc42 activation induced by chemokine stimulation, rescue experiments revealed that the GEF activity of DOCK8 was required for macrophage migration...
December 27, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28028151/lrch1-interferes-with-dock8-cdc42-induced-t-cell-migration-and-ameliorates-experimental-autoimmune-encephalomyelitis
#14
Xiaoyan Xu, Lei Han, Guixian Zhao, Shengjie Xue, Yunzhen Gao, Jun Xiao, Shicheng Zhang, Peng Chen, Zhi-Ying Wu, Jianping Ding, Ronggui Hu, Bin Wei, Hongyan Wang
Directional autoreactive CD4(+) T cell migration into the central nervous system plays a critical role in multiple sclerosis. Recently, DOCK8 was identified as a guanine-nucleotide exchange factor (GEF) for Cdc42 activation and has been associated with human mental retardation. Little is known about whether DOCK8 is related to multiple sclerosis (MS) and how to restrict its GEF activity. Using two screening systems, we found that LRCH1 competes with Cdc42 for interaction with DOCK8 and restrains T cell migration...
January 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28025315/%C3%AE-2-cop-is-involved-in-early-secretory-traffic-in-arabidopsis-and-is-required-for-plant-growth
#15
Fátima Gimeno-Ferrer, Noelia Pastor-Cantizano, César Bernat-Silvestre, Pilar Selvi-Martínez, Francisco Vera-Sirera, Caiji Gao, Miguel Angel Perez-Amador, Liwen Jiang, Fernando Aniento, María Jesús Marcote
COP (coat protein) I-coated vesicles mediate intra-Golgi transport and retrograde transport from the Golgi to the endoplasmic reticulum. These vesicles form through the action of the small GTPase ADP-ribosylation factor 1 (ARF1) and the COPI heptameric protein complex (coatomer), which consists of seven subunits (α-, β-, β'-, γ-, δ-, ε- and ζ-COP). In contrast to mammals and yeast, several isoforms for coatomer subunits, with the exception of γ and δ, have been identified in Arabidopsis. To understand the role of COPI proteins in plant biology, we have identified and characterized a loss-of-function mutant of α2-COP, an Arabidopsis α-COP isoform...
December 26, 2016: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28011692/different-endomembrane-trafficking-pathways-establish-apical-and-basal-polarities
#16
Ruixi Li, Cecilia Rodriguez Furlan, Junqi Wang, Wilhelmina van de Ven, Ting Gao, Natasha V Raikhel, Glenn R Hicks
The endomembrane system is an interconnected network required to establish signal transduction, cell polarity and cell shape in response to developmental or environmental stimuli. In the model plant Arabidopsis thaliana, there are numerous markers to visualize polarly localized plasma membrane proteins utilizing endomembrane trafficking. Previous studies have shown that the large ARF-GEF GNOM plays a key role in the establishment of basal polarity, whereas the apically polarized membrane proteins undergo sorting via different routes...
December 23, 2016: Plant Cell
https://www.readbyqxmd.com/read/28008853/ric-8a-a-g-protein-chaperone-with-nucleotide-exchange-activity-induces-long-range-secondary-structure-changes-in-g%C3%AE
#17
Ravi Kant, Baisen Zeng, Celestine J Thomas, Brian Bothner, Stephen R Sprang
Cytosolic Ric-8A has guanine nucleotide exchange factor (GEF) activity and is a chaperone for several classes of heterotrimeric G protein α subunits in vertebrates. Using Hydrogen-Deuterium Exchange-Mass Spectrometry (HDX-MS) we show that Ric-8A disrupts the secondary structure of the Gα Ras-like domain that girds the guanine nucleotide-binding site, and destabilizes the interface between the Gαi1 Ras and helical domains, allowing domain separation and nucleotide release. These changes are largely reversed upon binding GTP and dissociation of Ric-8A...
December 23, 2016: ELife
https://www.readbyqxmd.com/read/28003861/rei-1-a-novel-rab11-gef-with-a-sh3bp5-domain
#18
Aisa Sakaguchi, Miyuki Sato, Ken Sato
The small GTPase Rab proteins are key regulators of membrane trafficking. Rab11 is one of the best-characterized molecules among the Rab family proteins and it plays multiple roles in endocytic recycling, exocytosis, and cytokinesis. However, it remains unclear how Rab11 is activated at a precise timing and location and regulates its diverse functions. Specifically, our knowledge of the upstream regulatory factors that activate Rab11 is limited. In this regard, we have identified the RAB-11-interacting protein-1 (REI-1) as a novel guanine nucleotide exchange factor (GEF) for RAB-11 in Caenorhabditis elegans (C...
2016: Communicative & Integrative Biology
https://www.readbyqxmd.com/read/28003315/copi-trappii-activates-rab18-and-regulates-its-lipid-droplet-association
#19
Chunman Li, Xiaomin Luo, Shan Zhao, Gavin Ky Siu, Yongheng Liang, Hsiao Chang Chan, Ayano Satoh, Sidney Sb Yu
The transport protein particle (TRAPP) was initially identified as a vesicle tethering factor in yeast and as a guanine nucleotide exchange factor (GEF) for Ypt1/Rab1. In mammals, structures and functions of various TRAPP complexes are beginning to be understood. We found that mammalian TRAPPII was a GEF for both Rab18 and Rab1. Inactivation of TRAPPII-specific subunits by various methods including siRNA depletion and CRISPR-Cas9-mediated deletion reduced lipolysis and resulted in aberrantly large lipid droplets...
December 21, 2016: EMBO Journal
https://www.readbyqxmd.com/read/28002022/interface-analysis-of-small-gtp-binding-protein-complexes-suggests-preferred-membrane-orientations
#20
Ingrid R Vetter
Crystal structures of small GTP binding protein complexes with their effectors and regulators reveal that one particularly flat side of the G domain that contains helix α4 and the C-terminal helix α5 is practically devoid of contacts. Although this observation seems trivial since the main binding targets are the switch I and II regions opposite of this side, the fact that all interacting proteins, even the largest ones, seem to avoid occupying this area (except for Ran, that does not localize to membranes) is quite striking...
December 21, 2016: Biological Chemistry
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