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https://www.readbyqxmd.com/read/28065575/multiparametric-analysis-of-cell-shape-demonstrates-that-%C3%AE-pix-directly-couples-yap-activation-to-extracellular-matrix-adhesion
#1
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/28036092/human-rho-guanine-nucleotide-exchange-factor-11-arhgef11-regulates-dendritic-morphogenesis
#2
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/27991560/trpc3-gef-h1-axis-mediates-pressure-overload-induced-cardiac-fibrosis
#3
Takuro Numaga-Tomita, Naoyuki Kitajima, Takuya Kuroda, Akiyuki Nishimura, Kei Miyano, Satoshi Yasuda, Koichiro Kuwahara, Yoji Sato, Tomomi Ide, Lutz Birnbaumer, Hideki Sumimoto, Yasuo Mori, Motohiro Nishida
Structural cardiac remodeling, accompanying cytoskeletal reorganization of cardiac cells, is a major clinical outcome of diastolic heart failure. A highly local Ca(2+) influx across the plasma membrane has been suggested to code signals to induce Rho GTPase-mediated fibrosis, but it is obscure how the heart specifically decodes the local Ca(2+) influx as a cytoskeletal reorganizing signal under the conditions of the rhythmic Ca(2+) handling required for pump function. We found that an inhibition of transient receptor potential canonical 3 (TRPC3) channel activity exhibited resistance to Rho-mediated maladaptive fibrosis in pressure-overloaded mouse hearts...
December 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27986909/sos1-arhgef1-and-dock2-rho-gefs-mediate-jak-dependent-lfa-1-activation-by-chemokines
#4
Lara Toffali, Alessio Montresor, Michela Mirenda, Giorgio Scita, Carlo Laudanna
JAK-dependent activation of the rho module of integrin affinity triggering mediates chemokine-induced leukocyte adhesion. However, the signaling events linking JAKs to rho small GTPase activation by chemokines is still incompletely described. In this study, we show that son of sevenless 1 (SOS1), rho guanine nucleotide exchange factor (GEF)1 (ARHGEF1), and dedicator of cytokinesis (DOCK)2 GEFs mediate CXCL12-induced LFA-1 activation in human primary T lymphocytes. Downregulated expression of SOS1, ARHGEF1, and DOCK2 impairs LFA-1-mediated rapid T lymphocyte adhesion as well as underflow arrest on ICAM-1 induced by CXCL12...
December 16, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27934548/arhgef10-gene-polymorphism-is-closely-associated-with-the-risk-of-ischemic-stroke-in-northern-han-chinese-population
#5
Hong Li, Shasha Yu, Rui Wang, Zhaoqing Sun, Xinghu Zhou, Liqiang Zheng, Zhihua Yin, Xingang Zhang, Yingxian Sun
Stroke is a common disease with high mortality and morbidity. It is of high importance to identify biomarkers of stroke. Rho guanine nucleotide-exchange factor(GEF) 10 (ARHGEF10) gene polymorphism has been found to be associated with various human diseases, but its correlation with stroke remains unknown. This study aims to evaluate the potential association of the single nucleotide polymorphisms (SNPs) of ARHGEF10 with ischemic stroke (IS) in northern Han Chinese population. Three SNPs of ARHGEF10 gene were analyzed in 385 IS patients and 362 hypertension control patients using the ligase detection reaction (LDR) method...
February 2017: Neurological Research
https://www.readbyqxmd.com/read/27907191/trio-a-rho-family-gef-interacts-with-the-presynaptic-active-zone-proteins-piccolo-and-bassoon
#6
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/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/27854239/kshv-entry-and-trafficking-in-target-cells-hijacking-of-cell-signal-pathways-actin-and-membrane-dynamics
#8
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/27849131/spatial-rho-regulation-molecular-mechanisms-controlling-the-gap-protein-dlc3
#9
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
#10
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
#11
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/27816490/the-tumor-suppressor-cdx2-opposes-pro-metastatic-biomechanical-modifications-of-colon-cancer-cells-through-organization-of-the-actin-cytoskeleton
#12
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...
February 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27788493/multisite-phosphorylation-of-p-rex1-by-protein-kinase-c
#13
Juan Carlos Montero, Samuel Seoane, Sara García-Alonso, Atanasio Pandiella
P-Rex proteins are guanine nucleotide exchange factors (GEFs) that act on the Rho/Rac family of GTP binding proteins. The activity of P-Rex proteins is regulated by several extracellular stimuli. In fact, activation of growth factor receptors has been reported to activate a phosphorylation/dephosphorylation cycle of P-Rex1. Such cycle includes dephosphorylation of serines 313 and 319 which negatively regulate the GEF activity of P-Rex1, together with phosphorylation of serines 605 and 1169 which favour P-Rex1 GEF activity...
October 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27716788/vimar-is-a-novel-regulator-of-mitochondrial-fission-through-miro
#14
Lianggong Ding, Ye Lei, Yanping Han, Yuhong Li, Xunming Ji, Lei Liu
As fundamental processes in mitochondrial dynamics, mitochondrial fusion, fission and transport are regulated by several core components, including Miro. As an atypical Rho-like small GTPase with high molecular mass, the exchange of GDP/GTP in Miro may require assistance from a guanine nucleotide exchange factor (GEF). However, the GEF for Miro has not been identified. While studying mitochondrial morphology in Drosophila, we incidentally observed that the loss of vimar, a gene encoding an atypical GEF, enhanced mitochondrial fission under normal physiological conditions...
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27690729/endothelin-1-receptor-drives-invadopodia-exploiting-how-%C3%AE-arrestin-1-guides-the-way
#15
Anna Bagnato, Laura Rosanò
Metastatization is a complex multistep process requiring fine-tuned regulated cytoskeleton re-modeling, mediated by the cross-talk of actin with interacting partners, such as the Rho GTPases. Our expanding knowledge of invadopodia, small invasive membrane protrusions composed of a core of F-actin, actin regulators and actin-binding proteins, and hotspots for secretion of extracellular matrix (ECM) proteinases, contributes to clarify critical steps of the metastatic program. Growth factor receptors and their intermediate signaling molecules, along with matrix adhesion and rigidity, pH and hypoxia, act as drivers of cytoskeleton changes and invadopodia formation...
October 3, 2016: Small GTPases
https://www.readbyqxmd.com/read/27628050/rho-gtpases-regulation-and-roles-in-cancer-cell-biology
#16
Raquel B Haga, Anne J Ridley
Rho GTPases are well known for their roles in regulating cell migration, and also contribute to a variety of other cellular responses. They are subdivided into 2 groups: typical and atypical. The typical Rho family members, including RhoA, Rac1 and Cdc42, cycle between an active GTP-bound and inactive GDP-bound conformation, and are regulated by GEFs, GAPs and GDIs, whereas atypical Rho family members have amino acid substitutions that alter their ability to interact with GTP/GDP and hence are regulated by different mechanisms...
October 2016: Small GTPases
https://www.readbyqxmd.com/read/27617642/the-rho-guanine-nucleotide-exchange-factor-arhgef5-promotes-tumor-malignancy-via-epithelial-mesenchymal-transition
#17
Y Komiya, Y Onodera, M Kuroiwa, S Nomimura, Y Kubo, J-M Nam, K Kajiwara, S Nada, C Oneyama, H Sabe, M Okada
Epithelial tumor cells often acquire malignant properties, such as invasion/metastasis and uncontrolled cell growth, by undergoing epithelial-mesenchymal transition (EMT). However, the mechanisms by which EMT contributes to malignant progression remain elusive. Here we show that the Rho guanine nucleotide exchange factor (GEF) ARHGEF5 promotes tumor malignancy in a manner dependent on EMT status. We previously identified ARHGEF5, a member of the Dbl family of GEFs, as a multifunctional mediator of Src-induced cell invasion and tumor growth...
2016: Oncogenesis
https://www.readbyqxmd.com/read/27590342/role-of-cingulin-in-agonist-induced-vascular-endothelial-permeability
#18
Yufeng Tian, Grzegorz Gawlak, Xinyong Tian, Alok S Shah, Nicolene Sarich, Sandra Citi, Anna A Birukova
Agonist-induced activation of Rho GTPase signaling leads to endothelial cell (EC) permeability and may culminate in pulmonary edema, a devastating complication of acute lung injury. Cingulin is an adaptor protein first discovered in epithelium and is involved in the organization of the tight junctions. This study investigated the role of cingulin in control of agonist-induced lung EC permeability via interaction with RhoA-specific activator GEF-H1. The siRNA-induced cingulin knockdown augmented thrombin-induced EC permeability monitored by measurements of transendothelial electrical resistance and endothelial cell permeability for macromolecules...
November 4, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27573018/p66shc-couples-mechanical-signals-to-rhoa-through-fak-dependent-recruitment-of-p115-rhogef-and-gef-h1
#19
Ru-Feng Wu, Chengxu Liao, Guosheng Fu, Heather N Hayenga, Kejia Yang, Zhenyi Ma, Zhe Liu, Lance S Terada
Tissue cells respond to changes in tensional forces with proliferation or death through the control of RhoA. However, the response coupling mechanisms that link force with RhoA activation are poorly understood. We found that tension applied to fibronectin-coated microbeads caused recruitment of all three isoforms of the Shc adapter (p66(Shc), p52(Shc), and p46(Shc)) to adhesion complexes. The Shc PTB domain was necessary and sufficient for this recruitment, and screening studies revealed direct interactions with the FERM domain of FAK that were required for Shc translocation to adhesion complexes...
August 29, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27492682/rhogtpases-at-the-synapse-an-embarrassment-of-choice
#20
W Ba, N Nadif Kasri
Activity-dependent modifications in the strength of excitatory synapses are considered to be major cellular mechanisms that contribute to the plasticity of neuronal networks underlying learning and memory. Key mechanisms for the regulation of synaptic efficacy involve the dynamic changes in size and number of dendritic spines, as well as the synaptic incorporation and removal of AMPA-type glutamate receptors (AMPAr). As key regulators of the actin cytoskeleton, the Rho subfamily of GTP-binding proteins play a critical role in synaptic development and plasticity...
August 5, 2016: Small GTPases
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