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https://www.readbyqxmd.com/read/28736167/an-actomyosin-arf-gef-negative-feedback-loop-for-tissue-elongation-under-stress
#1
Junior J West, Teresa Zulueta-Coarasa, Janna A Maier, Donghoon M Lee, Ashley E E Bruce, Rodrigo Fernandez-Gonzalez, Tony J C Harris
In response to a pulling force, a material can elongate, hold fast, or fracture. During animal development, multi-cellular contraction of one region often stretches neighboring tissue. Such local contraction occurs by induced actomyosin activity, but molecular mechanisms are unknown for regulating the physical properties of connected tissue for elongation under stress. We show that cytohesins, and their Arf small G protein guanine nucleotide exchange activity, are required for tissues to elongate under stress during both Drosophila dorsal closure (DC) and zebrafish epiboly...
July 13, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28726538/marked-bleeding-diathesis-in-patients-with-platelet-dysfunction-due-to-a-novel-mutation-in-rasgrp2-encoding-caldag-gefi-p-gly305asp
#2
Emilse Bermejo, Maria F Alberto, David S Paul, Aaron A Cook, Paquita Nurden, Analia Sanchez Luceros, Alan T Nurden, Wolfgang Bergmeier
Congenital platelet function disorders are often the result of defects in critical signal transduction pathways required for platelet adhesion and clot formation. Mutations affecting RASGRP2, the gene encoding the Rap GTPase activator, CalDAG-GEFI, give rise to a novel, and rare, group of platelet signal transduction abnormalities. We here report platelet function studies for two brothers (P1 and P2) expressing a novel variant of RASGRP2, CalDAG-GEFI(p.Gly305Asp). P1 and P2 have a lifelong history of bleeding with severe epistaxis successfully treated with platelet transfusions or rFVIIa...
July 20, 2017: Platelets
https://www.readbyqxmd.com/read/28712859/tyr42-phosphorylation-of-rhoa-gtpase-promotes-tumorigenesis-through-nuclear-factor-nf-%C3%AE%C2%BAb
#3
Jae-Gyu Kim, Kyoung-Chan Choi, Chang-Won Hong, Hwee-Seon Park, Eun-Kyoung Choi, Yong-Sun Kim, Jae-Bong Park
Dysregulation of reactive oxygen species (ROS) levels is implicated in the pathogenesis of several diseases, including cancer. However, the molecular mechanisms of ROS in tumorigenesis have not been clearly elucidated. Hydrogen peroxide activated nuclear factor-κB (NF-κB) and RhoA GTPase. In particular, we found that hydrogen peroxide phosphorylated RhoA at Tyr42 via Src. P-Ty42 residue of RhoA was a binding site of Vav2, a guanine nucleotide exchange factor (GEF) that activates p-Tyr42 RhoA. P-Tyr42 RhoA then bound to IκB kinase γ (IKKγ), leading IKKβ activation...
July 13, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28710284/the-neuronal-protein-neurexin-directly-interacts-with-the-scribble-pix-complex-to-stimulate-f-actin-assembly-for-synaptic-vesicle-clustering
#4
Menglong Rui, Jinjun Qian, Lijuan Liu, Yihan Cai, Huihui Lv, Junhai Han, Zhengping Jia, Wei Xie
Synaptic vesicles (SVs) form distinct pools at synaptic terminals, and this well-regulated separation is necessary for normal neuro-transmission. However, how SV cluster in particular synaptic compartments to maintain normal neurotransmitter release remains a mystery. The presynaptic protein Neurexin (NRX) plays a significant role in synaptic architecture and function, and some evidences suggest that NRX is associated with neurological disorders, including autism spectrum disorders. However, the role of NRX in SV clustering is unclear...
July 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28706196/synaptic-gap-and-gef-complexes-cluster-proteins-essential-for-gtp-signaling
#5
Brent Wilkinson, Jing Li, Marcelo P Coba
GTPase-activating proteins (GAPs) and guanine exchange factors (GEFs) play essential roles in regulating the activity of small GTPases. Several GAPs and GEFs have been shown to be present at the postsynaptic density (PSD) within excitatory glutamatergic neurons and regulate the activity of glutamate receptors. However, it is not known how synaptic GAP and GEF proteins are organized within the PSD signaling machinery, if they have overlapping interaction networks, or if they associate with proteins implicated in contributing to psychiatric disease...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28701658/drosophila-dock-family-protein-zizimin-involves-in-pigment-cell-differentiation-in-pupal-retinae
#6
Fumito Ozasa, Kazushige Morishita, Ngoc Anh Suong Dang, Seiji Miyata, Hideki Yoshida, Masamitsu Yamaguchi
The dedicator of cytokinesis (DOCK) family proteins are known as one of guanine nucleotide exchange factors (GEFs), that contribute to cellular signaling processes by activating small G proteins. Although mammalian Zizimin is known to be a GEF for Cdc42 of Rho family small GTPase, its role in vivo is not well understood. Here we studied in vivo function of Drosophila Zizimin (Ziz). Knockdown of Ziz in eye imaginal discs induced the rough eye phenotype accompanied with fusion of ommatidia, loss of bristles and loss of pigments...
July 13, 2017: Cell Structure and Function
https://www.readbyqxmd.com/read/28696821/multifaceted-role-of-smcr8-as-autophagy-regulator
#7
Jennifer Jung, Christian Behrends
Through autophagy intracellular material is engulfed by double membrane vesicles and delivered to lysosomes for degradation. This process requires Rab GTPases, Rab GAPs and Rab GEFs for proper membrane trafficking, since they control vesicle budding, targeting and fusion. Deregulation of autophagy contributes to several human diseases including cancer, bacterial or viral infections and neurodegeneration. This review focuses on the complex roles of the newly identified protein SMCR8 and its interaction partners during formation and maturation of autophagosomes as well as regulation of lysosomal function and further discusses their implication in neurodegenerative diseases such as ALS and FTD...
July 11, 2017: Small GTPases
https://www.readbyqxmd.com/read/28682236/cell-cycle-entry-triggers-a-switch-between-two-modes-of-cdc42-activation-during-yeast-polarization
#8
Kristen L Witte, Devin Strickland, Michael Glotzer
Cell polarization underlies many cellular and organismal functions. The GTPase Cdc42 orchestrates polarization in many contexts. In budding yeast, polarization is associated with a focus of Cdc42•GTP which is thought to self sustain by recruiting a complex containing Cla4, a Cdc42-binding effector, Bem1, a scaffold, and Cdc24, a Cdc42 GEF. Using optogenetics, we probe yeast polarization and find that local recruitment of Cdc24 or Bem1 is sufficient to induce polarization by triggering self-sustaining Cdc42 activity...
July 6, 2017: ELife
https://www.readbyqxmd.com/read/28678686/cross-species-antiviral-activity-of-goose-interferon-lambda-against-duck-plague-virus-is-related-to-its-positive-self-regulatory-feedback-loop
#9
Shun Chen, Wei Zhang, Qin Zhou, Anqi Wang, Lipei Sun, Mingshu Wang, Renyong Jia, Dekang Zhu, Mafeng Liu, Kunfeng Sun, Qiao Yang, Ying Wu, Xiaoyue Chen, Anchun Cheng
Duck plague virus (DPV) is a virus of the Herpesviridae family that leads to acute disease with a high mortality rate in ducks. Control of the disease contributes to the development of poultry breeding. Type III IFN family (IFN-λs) is a novel member of the IFN family, and goose IFN-λ (goIFN-λ) is a newly identified gene whose antiviral function has only been investigated to a limited extent. Here, the cross-species antiviral activity of goIFN-λ against DPV in duck embryo fibroblasts (DEFs) was studied. We found that pre-treatment with goIFN-λ greatly increased the expression of IFN-λ in both heterologous DEFs and homologous goose embryo fibroblasts (GEFs), while differentially inducing IFNα- and IFN-stimulated genes...
June 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28674249/effects-of-gintonin-enriched-fraction-in-an-atopic-dermatitis-animal-model-involvement-of-autotaxin-regulation
#10
Byung-Hwan Lee, Ho-Kyoung Kim, Minhee Jang, Hyeon-Joong Kim, Sun-Hye Choi, Sung-Hee Hwang, Hyoung-Chun Kim, Hyewhon Rhim, Ik-Hyun Cho, Seung-Yeol Nah
Ginseng extract has been used for prevention of atopic dermatitis (AD) in experimental animal models. However, little is known about its active ingredients and the molecular mechanisms underlying its anti-AD effects. Recently, we isolated a unique lysophosphatidic acid (LPA) receptor ligand, gintonin, from ginseng. Gintonin, the glycolipoprotein fraction of ginseng, contains LPAs, mainly LPA C18 : 2 with other minor lysophospholipid components. A line of evidence showed that serum autotaxin (ATX) activity and level are significantly elevated in human AD patients compared to those in normal controls, which indicates that ATX may be involved in human AD...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28666462/two-distinct-mtorc2-dependent-pathways-converge-on-rac1-to-drive-breast-cancer-metastasis
#11
Meghan Morrison Joly, Michelle M Williams, Donna J Hicks, Bayley Jones, Violeta Sanchez, Christian D Young, Dos D Sarbassov, William J Muller, Dana Brantley-Sieders, Rebecca S Cook
BACKGROUND: The importance of the mTOR complex 2 (mTORC2) signaling complex in tumor progression is becoming increasingly recognized. HER2-amplified breast cancers use Rictor/mTORC2 signaling to drive tumor formation, tumor cell survival and resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapy. Cell motility, a key step in the metastatic process, can be activated by mTORC2 in luminal and triple negative breast cancer cell lines, but its role in promoting metastases from HER2-amplified breast cancers is not yet clear...
June 30, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28664031/large-scale-structural-alteration-of-brain-in-epileptic-children-with-scn1a-mutation
#12
Yun-Jeong Lee, Mi-Sun Yum, Min-Jee Kim, Woo-Hyun Shim, Hee Mang Yoon, Il Han Yoo, Jiwon Lee, Byung Chan Lim, Ki Joong Kim, Tae-Sung Ko
OBJECTIVE: Mutations in SCN1A gene encoding the alpha 1 subunit of the voltage gated sodium channel are associated with several epilepsy syndromes including genetic epilepsy with febrile seizures plus (GEFS +) and severe myoclonic epilepsy of infancy (SMEI). However, in most patients with SCN1A mutation, brain imaging has reported normal or non-specific findings including cerebral or cerebellar atrophy. The aim of this study was to investigate differences in brain morphometry in epileptic children with SCN1A mutation compared to healthy control subjects...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28663287/carmil-family-proteins-as-multidomain-regulators-of-actin-based-motility
#13
Benjamin C Stark, M Hunter Lanier, John A Cooper
CARMILs are large multidomain proteins that regulate the actin-binding activity of capping protein (CP), a major capper of actin filament barbed ends in cells. CARMILs bind directly to CP and induce a conformational change that allosterically decreases but does not abolish its actin-capping activity. The CP-binding domain of CARMIL consists of the CP-interaction (CPI) and CARMIL-specific interaction (CSI) motifs, which are arranged in tandem. Many cellular functions of CARMILs require the interaction with CP; however, a more surprising result is that the cellular function of CP in cells appears to require binding to a CARMIL or another protein with a CPI motif, suggesting that CPI-motif proteins target CP and modulate its actin-capping activity...
July 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28662881/sperm-membrane-proteins-associated-with-the-boar-semen-cryopreservation
#14
Daianny B Guimarães, Tatyane B Barros, Maurício F van Tilburg, Jorge A M Martins, Arlindo A Moura, Frederico B Moreno, Ana C Monteiro-Moreira, Renato A Moreira, Ricardo Toniolli
This study aimed to define sperm membrane protein markers of semen freezability of boars with the aid of a proteomic approach. Semen from fourteen adult boars were subjected to slow freezing and rapid thawing. After thawing, sperm vigor and motility were analyzed, and based on these results, animals were separated into two groups: good (GFEs) and poor freezability (PFEs). Sperm membrane proteins were extracted and subjected to two-dimensional electrophoresis. Stained gels were analyzed by computerized resources to indicate differentially expressed protein spots, that were identified by mass spectrometry...
June 20, 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28657426/oncogenic-ect2-signaling-regulates-rrna-synthesis-in-nsclc
#15
Verline Justilien, Kayla C Lewis, Nicole R Murray, Alan P Fields
The Rho GTPase family members Rac1, Cdc42 and RhoA play key contributory roles in the transformed phenotype of human cancers. Epithelial Cell Transforming Sequence 2 (Ect2), a guanine nucleotide exchange factor (GEF) for these Rho GTPases, has also been implicated in a variety of human cancers. We have shown that Ect2 is frequently overexpressed in both major forms of non-small cell lung cancer (NSCLC), lung adenocarcinoma (LADC) and lung squamous cell carcinoma (LSCC), which together make up approximately 70% of all lung cancer diagnoses...
June 28, 2017: Small GTPases
https://www.readbyqxmd.com/read/28652571/discovery-of-long-range-inhibitory-signaling-to-ensure-single-axon-formation
#16
Tetsuya Takano, Mengya Wu, Shinichi Nakamuta, Honda Naoki, Naruki Ishizawa, Takashi Namba, Takashi Watanabe, Chundi Xu, Tomonari Hamaguchi, Yoshimitsu Yura, Mutsuki Amano, Klaus M Hahn, Kozo Kaibuchi
A long-standing question in neurodevelopment is how neurons develop a single axon and multiple dendrites from common immature neurites. Long-range inhibitory signaling from the growing axon is hypothesized to prevent outgrowth of other immature neurites and to differentiate them into dendrites, but the existence and nature of this inhibitory signaling remains unknown. Here, we demonstrate that axonal growth triggered by neurotrophin-3 remotely inhibits neurite outgrowth through long-range Ca(2+) waves, which are delivered from the growing axon to the cell body...
June 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28644070/particulate-matter-disrupts-human-lung-endothelial-cell-barrier-integrity-via-rho-dependent-pathways
#17
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/28641070/elmo-proteins-transduce-g-protein-coupled-receptor-signal-to-control-reorganization-of-actin-cytoskeleton-in-chemotaxis-of-eukaryotic-cells
#18
Xuehua Xu, Tian Jin
Chemotaxis, which is chemoattractant-guided directional cell migration, plays major roles in recruitment of neutrophils, the metastasis of cancer cells, and the development of the model organism Dictyostelium discoideum. These cells share remarkable similarities in the signaling pathways by which they control chemotaxis. They all use a G protein-coupled receptor (GPCR)-mediated signal transduction pathway to sense the chemotactic gradient to guide cell migration. Diverse chemokines activate Rac through conserved GPCR signaling pathways...
June 22, 2017: Small GTPases
https://www.readbyqxmd.com/read/28632484/rab-gtpases-and-their-interacting-protein-partners-structural-insights-into-rab-functional-diversity
#19
Olena Pylypenko, Hussein Hammich, I-Mei Yu, Anne Houdusse
Rab molecular switches are key players in defining membrane identity and regulating intracellular trafficking events in eukaryotic cells. In spite of their global structural similarity, Rab-family members acquired particular features that allow them to perform specific cellular functions. The overall fold and local sequence conservations enable them to utilize a common machinery for prenylation and recycling; while individual Rab structural differences determine interactions with specific partners such as GEFs, GAPs and effector proteins...
June 20, 2017: Small GTPases
https://www.readbyqxmd.com/read/28630074/the-enterohaemorrhagic-escherichia-coli-effector-espw-triggers-actin-remodeling-in-a-rac1-dependent-manner
#20
Pamela Sandu, Valerie F Crepin, Hauke Drechsler, Andrew D McAinsh, Gad Frankel, Cedric N Berger
Enterohaemorrhagic Escherichia coli (EHEC) is a diarrheagenic pathogen that colonizes the gut mucosa and induces attaching-and-effacing lesions. EHEC employs a type III secretion system (T3SS) to translocate 50 effector proteins that hijack and manipulate host cell signalling pathways, which allow bacterial colonization, subversion of immune responses and disease progression. The aim of this study was to characterize the T3SS effector EspW. We found espW in the sequenced O157:H7 and non-O157 EHEC strains as well as in Shigella boydii Furthermore, a truncated version of EspW, containing the first 206 residues is present in EPEC strains belonging to serotype O55:H7...
June 19, 2017: Infection and Immunity
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