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https://www.readbyqxmd.com/read/29453282/eukaryotic-translation-elongation-factor-2-eef2-catalyzes-reverse-translocation-of-the-eukaryotic-ribosome
#1
Denis Susorov, Nikita Zakharov, Ekaterina Shuvalova, Alexander Ivanov, Tatiana Egorova, Alexey Shuvalov, Ivan N Shatsky, Elena Alkalaeva
During protein synthesis, a ribosome moves along the mRNA template and, using aminoacyl-tRNAs, decodes the template nucleotide triplets to assemble a protein amino acid sequence. This movement is accompanied by shifting of mRNA-tRNA complexes within the ribosome in a process called translocation. In living cells, this process proceeds in a unidirectional manner, bringing the ribosome to the 3'-end of mRNA, and is catalyzed by the GTPase translation elongation factor 2 (EF-G in prokaryotes, eEF2 in eukaryotes)...
February 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29452030/comparative-phylogenetic-and-expression-analysis-of-small-gtpases-families-in-legume-and-non-legume-plants
#2
Ana Claudia Flores, Virginia Dalla Via, Virginia Savy, Ulises Mancini Villagra, María Eugenia Zanetti, Flavio Blanco
BACKGROUND: Small monomeric GTPases act as molecular switches in several processes that involve polar cell growth, participating mainly in vesicle trafficking and cytoskeleton rearrangements. This gene superfamily has largely expanded in plants through evolution as compared with other Kingdoms, leading to the suggestion that members of each subfamily might have acquired new functions associated to plant-specific processes. Legume plants engage in a nitrogen-fixing symbiotic interaction with rhizobia in a process that involves polar growth processes associated with the infection throughout the root hair...
February 16, 2018: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/29447953/dendrite-growth-and-the-effect-of-ectopic-rheb-expression-on-cortical-neurons
#3
Aidan M Sokolov, Caitlin M Seluzicki, Mary C Morton, David M Feliciano
Ras homology enriched in brain (Rheb) is a GTPase that activates the protein kinase mammalian Target of Rapamycin (mTOR). Rheb mutations cause intellectual delay and megalencephaly. mTOR hyperactivation causes a constellation of neurodevelopmental disorders called "mTOR-opathies" that are frequently accompanied by hyperexcitable cortical malformations. Cortical malformations within the anterior cingulate cortex (ACC) and somatosensory cortex (SSC) frequently colocalize with hyperexcitability. Although Rheb and mTOR are implicated in the formation of cortical lesions, seizure activity, and defects in neuronal migration, the contribution of Rheb to changes in neuron size and dendrite morphology is not well established...
February 12, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29445151/the-vesicle-trafficking-regulator-pn_scd1-is-demethylated-and-overexpressed-in-florets-of-apomictic-paspalum-notatum-genotypes
#4
Marika Bocchini, Giulio Galla, Fulvio Pupilli, Michele Bellucci, Gianni Barcaccia, Juan Pablo A Ortiz, Silvina C Pessino, Emidio Albertini
Apomixis (asexual reproduction through seeds) is considered a deviation of the sexual reproductive pathway leading to the development of clonal progenies genetically identical to the mother plant. Here we used the Methylation-Sensitive Amplification Polymorphism (MSAP) technique to characterize cytosine methylation patterns occurring in florets of sexual and aposporous Paspalum notatum genotypes, in order to identify epigenetically-controlled genes putatively involved in apomixis development. From twelve polymorphic MSAP-derived sequences, one (PN_6...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29444419/pak1-kinase-maintains-apical-membrane-identity-in-epithelia
#5
Mario Aguilar-Aragon, Ahmed Elbediwy, Valentina Foglizzo, Georgina C Fletcher, Vivian S W Li, Barry J Thompson
Epithelial cells are polarized along their apical-basal axis by the action of the small GTPase Cdc42, which is known to activate the aPKC kinase at the apical domain. However, loss of aPKC kinase activity was reported to have only mild effects on epithelial cell polarity. Here, we show that Cdc42 also activates a second kinase, Pak1, to specify apical domain identity in Drosophila and mammalian epithelia. aPKC and Pak1 phosphorylate an overlapping set of polarity substrates in kinase assays. Inactivating both aPKC kinase activity and the Pak1 kinase leads to a complete loss of epithelial polarity and morphology, with cells losing markers of apical polarization such as Crumbs, Par3/Bazooka, or ZO-1...
February 13, 2018: Cell Reports
https://www.readbyqxmd.com/read/29444302/rab-gtpases-in-the-basal-land-plant-marchantia-polymorpha
#6
Naoki Minamino, Takehiko Kanazawa, Atsuko Era, Kazuo Ebine, Akihiko Nakano, Takashi Ueda
The RAB GTPase is an evolutionarily conserved machinery component of membrane trafficking, which is the fundamental system for cell viability and higher-order biological functions. The composition of RAB GTPases in each organism is closely related to the complexity and organization of the membrane-trafficking pathway, which has been developed uniquely to realize the organism-specific membrane trafficking system. Comparative genomics has suggested that terrestrialization and/or multicellularization were associated with the expansion of membrane trafficking pathways in green plants, which has yet to be validated in basal land plant lineages...
February 10, 2018: Plant & Cell Physiology
https://www.readbyqxmd.com/read/29444209/geranylgeranyl-pyrophosphate-synthase-facilitates-the-organization-of-cardiomyocytes-during-mid-gestation-through-modulating-protein-geranylgeranylation-in-mouse-heart
#7
Zhong Chen, Na Xu, Danyang Chong, Shan Guan, Chen Jiang, Zhongzhou Yang, Chaojun Li
Aims: With the maturation of placenta, ventricular chamber maturation enhances cardiac contractile performance to adapt to the metabolic demand of growing embryo. The organization of cardiomyocytes is required for the morphological remodeling in ventricular chamber maturation. However, the mechanism governing the establishment of cardiac cytoarchitecture during ventricular chamber maturation is still poorly studied. Methods and results: Here, we found that the expression of geranylgeranyl pyrophosphate synthase (Ggpps), which mediates protein geranylgeranylation, increased in the mouse heart after the onset of placental function...
February 12, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29441061/profiling-of-human-molecular-pathways-affected-by-retrotransposons-at-the-level-of-regulation-by-transcription-factor-proteins
#8
Daniil Nikitin, Dmitry Penzar, Andrew Garazha, Maxim Sorokin, Victor Tkachev, Nicolas Borisov, Alexander Poltorak, Vladimir Prassolov, Anton A Buzdin
Endogenous retroviruses and retrotransposons also termed retroelements (REs) are mobile genetic elements that were active until recently in human genome evolution. REs regulate gene expression by actively reshaping chromatin structure or by directly providing transcription factor binding sites (TFBSs). We aimed to identify molecular processes most deeply impacted by the REs in human cells at the level of TFBS regulation. By using ENCODE data, we identified ~2 million TFBS overlapping with putatively regulation-competent human REs located in 5-kb gene promoter neighborhood (~17% of all TFBS in promoter neighborhoods; ~9% of all RE-linked TFBS)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29440639/the-small-gtpase-rhou-lays-downstream-of-jak-stat-signaling-and-mediates-cell-migration-in-multiple-myeloma
#9
Sara Canovas Nunes, Martina Manzoni, Marco Pizzi, Elisa Mandato, Marilena Carrino, Laura Quotti Tubi, Renato Zambello, Fausto Adami, Andrea Visentin, Gregorio Barilà, Livio Trentin, Sabrina Manni, Antonino Neri, Gianpietro Semenzato, Francesco Piazza
Multiple myeloma is a post-germinal center B-cell neoplasm, characterized by the proliferation of malignant bone marrow plasma cells, whose survival and proliferation is sustained by growth factors and cytokines present in the bone marrow microenvironment. Among them, IL-6 triggers the signal downstream of its receptor, leading to the activation of the JAK/STAT pathway. The atypical GTPase RhoU lays downstream of STAT3 transcription factor and could be responsible for mediating its effects on cytoskeleton dynamics...
February 13, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29440144/spon2-promotes-m1-like-macrophage-recruitment-and-inhibits-hepatocellular-carcinoma-metastasis-by-distinct-integrin-rho-gtpase-hippo-pathways
#10
Yan-Li Zhang, Qing Li, Xiao-Mei Yang, Fang Fang, Jun Li, Ya-Hui Wang, Qin Yang, Lei Zhu, Hui-Zhen Nie, Xue-Li Zhang, Ming-Xuan Feng, Shu-Heng Jiang, Guang-Ang Tian, Li-Peng Hu, Ho-Young Lee, Su-Jae Lee, Qiang Xia, Zhi-Gang Zhang
Tumor-associated macrophages (TAM) represent key regulators of the complex interplay between cancer and the immune microenvironment. Matricellular protein SPON2 is essential for recruiting lymphocytes and initiating immune responses. Recent studies have shown that SPON2 has complicated roles in cell migration and tumor progression. Here we report that, in the tumor microenvironment of hepatocellular carcinoma (HCC), SPON2 not only promotes infiltration of M1-like macrophages but also inhibits tumor metastasis...
February 13, 2018: Cancer Research
https://www.readbyqxmd.com/read/29439717/dysregulated-phosphorylation-of-rab-gtpases-by-lrrk2-induces-neurodegeneration
#11
Ga Ram Jeong, Eun-Hae Jang, Jae Ryul Bae, Soyoung Jun, Ho Chul Kang, Chi-Hu Park, Joo-Ho Shin, Yukio Yamamoto, Keiko Tanaka-Yamamoto, Valina L Dawson, Ted M Dawson, Eun-Mi Hur, Byoung Dae Lee
BACKGROUND: Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial and sporadic Parkinson's disease (PD). Elevated kinase activity is associated with LRRK2 toxicity, but the substrates that mediate neurodegeneration remain poorly defined. Given the increasing evidence suggesting a role of LRRK2 in membrane and vesicle trafficking, here we systemically screened Rab GTPases, core regulators of vesicular dynamics, as potential substrates of LRRK2 and investigated the functional consequence of such phosphorylation in cells and in vivo...
February 13, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29438442/the-sirna-mediated-knockdown-of-glun3a-in-46c-derived-neural-stem-cells-affects-mrna-expression-levels-of-neural-genes-including-known-iglur-interactors
#12
Svenja Pachernegg, Sebastian Eilebrecht, Elke Eilebrecht, Hendrik Schöneborn, Sebastian Neumann, Arndt G Benecke, Michael Hollmann
For years, GluN3A was solely considered to be a dominant-negative modulator of NMDARs, since its incorporation into receptors alters hallmark features of conventional NMDARs composed of GluN1/GluN2 subunits. Only recently, increasing evidence has accumulated that GluN3A plays a more diversified role. It is considered to be critically involved in the maturation of glutamatergic synapses, and it might act as a molecular brake to prevent premature synaptic strengthening. Its expression pattern supports a putative role during neural development, since GluN3A is predominantly expressed in early pre- and postnatal stages...
2018: PloS One
https://www.readbyqxmd.com/read/29437779/the-elmo-mbc-complex-and-rhogap19d-couple-rho-family-gtpases-during-mesenchymal-to-epithelial-like-transitions
#13
Christopher P Toret, Pruthvi C Shivakumar, Pierre-François Lenne, Andre Le Bivic
Many metazoan developmental processes require cells to transition between migratory mesenchymal- and adherent epithelial-like states. These transitions require Rho GTPase-mediated actin rearrangements downstream of integrin and cadherin pathways. A regulatory toolbox of GEF and GAP proteins precisely coordinates Rho protein activities, yet defining the involvement of specific regulators within a cellular context remains a challenge due to overlapping and coupled activities. Here we demonstrate that Drosophila dorsal closure is a powerful model for Rho GTPase regulation during transitions from leading edges to cadherin contacts...
February 2, 2018: Development
https://www.readbyqxmd.com/read/29437579/mouse-platelet-ral-gtpases-control-p-selectin-surface-expression-regulating-platelet-leukocyte-interaction
#14
Andreas Wersäll, Chris M Williams, Edward Brown, Tommaso Iannitti, Neil Williams, Alastair W Poole
OBJECTIVE: RalA and RalB GTPases are important regulators of cell growth, cancer metastasis, and granule secretion. The purpose of this study was to determine the role of Ral GTPases in platelets with the use of platelet-specific gene-knockout mouse models. APPROACH AND RESULTS: This study shows that platelets from double knockout mice, in which both GTPases have been deleted, show markedly diminished (≈85% reduction) P-selectin translocation to the surface membrane, suggesting a critical role in α-granule secretion...
February 8, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29435114/ras-gtpases-are-modified-by-sumoylation
#15
Byeong Hyeok Choi, Changyan Chen, Mark Philips, Wei Dai
RAS proteins are GTPases that participate in multiple signal cascades, regulating crucial cellular processes including cell survival, proliferation, differentiation, and autophagy. Mutations or deregulated activities of RAS are frequently the driving force for oncogenic transformation and tumorigenesis. Given the important roles of the small ubiquitin-related modifier (SUMO) pathway in controlling the stability, activity, or subcellular localization of key cellular regulators, we investigated here whether RAS proteins are posttranslationally modified (i...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29434926/pak5-overexpression-is-associated-with-lung-metastasis-in-osteosarcoma
#16
Kun Han, Yan Zhou, Kuo-Fu Tseng, Haiyan Hu, Kunpeng Li, Yaling Wang, Zhihua Gan, Shuchen Lin, Yongning Sun, Daliu Min
p21-activated kinases (PAKs) are multifunctional effectors of Rho GTPases, which are associated with cytoskeletal organization, cellular morphogenesis, migration and survival. PAKs are overactive in a number of tumor tissues and have attracted attention as a potential target for cancer therapy. In the present study, PAK5 levels were analyzed in primary osteosarcoma (OS) samples (n=65) using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) methods. In the primary OS tissue, increased PAK5 expression (IHC score >2, n=37) was associated with significantly decreased overall survival (P=0...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434248/modulation-of-small-gtpase-activity-by-nme-proteins
#17
REVIEW
Vedrana Filić, Maja Marinović, Marko Šoštar, Igor Weber
NME proteins are reported to influence signal transduction activity of small GTPases from the Ras superfamily by diverse mechanisms in addition to their generic NDP kinase activity, which replenishes the cytoplasmic pool of GTP. Comprehensive evidence shows that NME proteins modulate the activity of Ras GTPases, in particular members of the Rho family, via binding to their major activators GEFs. Direct interaction between several NMEs and Ras GTPases were also indicated in vitro and in vivo. These modes of regulation are mainly independent of the NME's kinase activity...
February 12, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29433439/legionella-effector-ankx-interacts-with-host-nuclear-protein-plekhn1
#18
Xiaobo Yu, Rebecca R Noll, Barbara P Romero Dueñas, Samual C Allgood, Kristi Barker, Jeffrey L Caplan, Matthias P Machner, Joshua LaBaer, Ji Qiu, M Ramona Neunuebel
BACKGROUND: The intracellular bacterial pathogen Legionella pneumophila proliferates in human alveolar macrophages, resulting in a severe pneumonia termed Legionnaires' disease. Throughout the course of infection, L. pneumophila remains enclosed in a specialized membrane compartment that evades fusion with lysosomes. The pathogen delivers over 300 effector proteins into the host cell, altering host pathways in a manner that sets the stage for efficient pathogen replication. The L. pneumophila effector protein AnkX targets host Rab GTPases and functions in preventing fusion of the Legionella-containing vacuole with lysosomes...
January 5, 2018: BMC Microbiology
https://www.readbyqxmd.com/read/29432743/the-inhibition-of-the-effect-and-mechanism-of-vascular-intimal-hyperplasia-in-tiam1-knockout-mice
#19
Wenxin Kou, Xu Xu, Shuya Ji, Mengyao Chen, Dongdong Liu, Kai Wang, Jianhui Zhuang, Qing Yu, Qian Zhao, Yawei Xu, Hongli Zhang, Wenhui Peng
T-Cell Lymphoma Invasion and Metastasis 1 (Tiam1) is a specific nucleotide exchange factor (GEF) that can activate Rho-like GTPase and Rac1 and regulate various cellular processes, including cell cycle progression and cell migration. The roles of Tiam1 in vascular intimal hyperplasia, especially in vascular smooth muscle cell proliferation and migration, are not fully understood. In this study, we investigated the effect of Tiam1 on vascular intimal hyperplasia in a carotid artery ligation model and human aortic smooth muscle cells (HASMCs)...
February 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29432733/dock1-inhibition-suppresses-cancer-cell-invasion-and-macropinocytosis-induced-by-self-activating-rac1p29s-mutation
#20
Takahiro Tomino, Hirotada Tajiri, Takaaki Tatsuguchi, Takahiro Shirai, Kounosuke Oisaki, Shigeki Matsunaga, Fumiyuki Sanematsu, Daiji Sakata, Tomoharu Yoshizumi, Yoshihiko Maehara, Motomu Kanai, Jean-François Cote, Yoshinori Fukui, Takehito Uruno
Rac1 is a member of the Rho family of small GTPases that regulates cytoskeletal reorganization, membrane polarization, cell migration and proliferation. Recently, a self-activating mutation of Rac1, Rac1P29S, has been identified as a recurrent somatic mutation frequently found in sun-exposed melanomas, which possesses increased inherent GDP/GTP exchange activity and cell transforming ability. However, the role of cellular Rac1-interacting proteins in the transforming potential of Rac1P29S remains unclear. We found that the catalytic domain of DOCK1, a Rac-specific guanine nucleotide exchange factor (GEF) implicated in malignancy of a variety of cancers, can greatly accelerate the GDP/GTP exchange of Rac1P29S...
February 9, 2018: Biochemical and Biophysical Research Communications
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