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Rho GTPases

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https://www.readbyqxmd.com/read/28920944/the-dosage-dependent-effect-exerted-by-the-nm23-h1-h2-homolog-ndk-1-on-distal-tip-cell-migration-in-c-elegans
#1
Zsolt Farkas, Luca Fancsalszky, Éva Saskői, Alexandra Gráf, Krisztián Tárnok, Anil Mehta, Krisztina Takács-Vellai
Abnormal regulation of cell migration and altered rearrangement of the cytoskeleton are fundamental properties of metastatic cells. The first identified metastasis suppressor NM23-H1, which displays nucleoside-diphosphate kinase (NDPK) activity is involved in these processes. NM23-H1 inhibits the migratory and invasive potential of some cancer cells. Correspondingly, numerous invasive cancer cell lines (eg, breast, colon, oral, hepatocellular carcinoma, and melanoma) display low endogenous NM23 levels. In this review, we summarize mechanisms, which are linked to the anti-metastatic activity of NM23...
September 18, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28916556/cell-scientist-to-watch-paul-timpson
#2
(no author information available yet)
Paul Timpson received his bachelor's degree from the University of Strathclyde, UK and completed his PhD under the supervision of Margaret Frame at the Beatson Institute for Cancer Research and the University of Glasgow in 2002, working on Src kinases and Rho family GTPases in cancer cell invasion. He then moved to the Garvan Institute of Medical Research in Sydney, Australia to work with Roger Daly on the actin-binding protein cortactin in several cancer models. Paul returned to the Beatson Institute in 2007 with the aid of an AstraZeneca postdoctoral research fellowship...
September 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28912560/the-srgap2-snps-their-haplotypes-and-g%C3%A2-%C3%A3-%C3%A2-e-interactions-on-serum-lipid-traits
#3
Liu Miao, Rui-Xing Yin, Jin-Zhen Wu, Shuo Yang, Wei-Xiong Lin, Shang-Ling Pan
Maonan nationality is a relatively conservative and isolated minority in China. Little is known about the association of the Slit-Robo Rho GTPase activating protein 2 gene (SRGAP2) single nucleotide polymorphisms (SNPs) and serum lipid levels in the Chinese populations. This study was performed to clarify the association of the SRGAP2 rs2483058 and rs2580520 SNPs and their haplotypes with serum lipid traits in the Maonan and Han populations. Genotyping of the 2 SNPs was performed in 2444 unrelated subjects (Han, 1210 and Maonan, 1234) by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912272/the-transcription-factor-hoxb7-regulates-erk-kinase-activity-and-thereby-stimulates-the-motility-and-invasiveness-of-pancreatic-cancer-cells
#4
Makiko Tsuboi, Keisuke Taniuchi, Takahiro Shimizu, Motoaki Saito, Toshiji Saibara
HOX genes encode transcription factors that function as sequence-specific transcription factors that are involved in cellular proliferation, differentiation, and death. The aim of this study was to investigate the role of a HOX family protein, HOXB7, in the motility and invasiveness of pancreatic cancer cells. We previously identified a HOXB7 transcript that is one of a number of transcripts that are preferentially translated in membrane protrusions in pancreatic cancer cells. Immunocytochemistry showed that HOXB7 was localized to the cell protrusions of migrating pancreatic cancer cells...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28911825/paving-the-rho-in-cancer-metastasis-rho-gtpases-and-beyond
#5
REVIEW
Sepp Jansen, Reinoud Gosens, Thomas Wieland, Martina Schmidt
Malignant carcinomas are often characterized by metastasis, the movement of carcinoma cells from a primary site to colonize distant organs. For metastasis to occur, carcinoma cells first must adopt a pro-migratory phenotype and move through the surrounding stroma towards a blood or lymphatic vessel. Currently, there are very limited possibilities to target these processes therapeutically. The family of Rho GTPases is an ubiquitously expressed division of GTP-binding proteins involved in the regulation of cytoskeletal dynamics and intracellular signaling...
September 11, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28894085/p190rhogap-proteins-contain-pseudogtpase-domains
#6
Amy L Stiegler, Titus J Boggon
The two p190RhoGAP proteins, p190RhoGAP-A and -B, are key regulators of Rho GTPase signaling and are essential for actin cytoskeletal structure and contractility. Here we report the discovery of two evolutionarily conserved GTPase-like domains located in the 'middle domain', previously thought to be unstructured. Deletion of these domains reduces RhoGAP activity. Crystal structures, MANT-GTPγS binding, thermal denaturation, biochemical assays and sequence homology analysis all strongly support defects in nucleotide-binding activity...
September 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28894027/activation-status-coupled-transient-s-acylation-determines-membrane-partitioning-of-a-plant-rho-related-gtpase
#7
Nadav Sorek, Limor Poraty, Hasana Sternberg, Ella Buriakovsky, Einat Bar, Efraim Lewinsohn, Shaul Yalovsky
ROPs or RACs are plant Rho-related GTPases implicated in regulation of multitude of signaling pathways that function at the plasma membrane via posttranslational lipid modifications. The relations between ROP activation status and their membrane localization has not been established. Here, we show that endogenous ROPs, as well as a transgenic His6:GFP:AtROP6 fusion protein, were partitioned between Triton X-100 soluble and insoluble membranes. In contrast, the His6:GFP:Atrop6(CA) activated mutant accumulated exclusively in detergent resistant membranes...
September 11, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28889942/differential-functions-of-wave-regulatory-complex-subunits-in-the-regulation-of-actin-driven-processes
#8
Christof Litschko, Joern Linkner, Stefan Brühmann, Theresia E B Stradal, Tobias Reinl, Lothar Jänsch, Klemens Rottner, Jan Faix
The WAVE regulatory complex (WRC) links upstream Rho-family GTPase signaling to the activation of the ARP2/3 complex in different organisms. WRC-induced and ARP2/3 complex-mediated actin nucleation beneath the plasma membrane is critical for actin assembly in the leading edge to drive efficient cell migration. The WRC is a stable heteropentamer composed of SCAR/WAVE, Abi, Nap, Pir and the small polypeptide Brk1/Hspc300. Functional interference with individual subunits of the complex frequently results in diminished amounts of the remaining polypeptides of the WRC complex, implying the complex to act as molecular entity...
September 4, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28887403/the-functions-of-reelin-in-membrane-trafficking-and-cytoskeletal-dynamics-implications-for-neuronal-migration-polarization-and-differentiation
#9
REVIEW
Jessica Santana, María-Paz Marzolo
Reelin is a large extracellular matrix protein with relevant roles in mammalian central nervous system including neurogenesis, neuronal polarization and migration during development; and synaptic plasticity with its implications in learning and memory, in the adult. Dysfunctions in reelin signaling are associated with brain lamination defects such as lissencephaly, but also with neuropsychiatric diseases like autism, schizophrenia and depression as well with neurodegeneration. Reelin signaling involves a core pathway that activates upon reelin binding to its receptors, particularly ApoER2 (apolipoprotein E receptor 2)/LRP8 (low-density lipoprotein receptor-related protein 8) and very low-density lipoprotein receptor, followed by Src/Fyn-mediated phosphorylation of the adaptor protein Dab1 (Disabled-1)...
September 7, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28886345/rac1-missense-mutations-in-developmental-disorders-with-diverse-phenotypes
#10
Margot R F Reijnders, Nurhuda M Ansor, Maria Kousi, Wyatt W Yue, Perciliz L Tan, Katie Clarkson, Jill Clayton-Smith, Ken Corning, Julie R Jones, Wayne W K Lam, Grazia M S Mancini, Carlo Marcelis, Shehla Mohammed, Rolph Pfundt, Maian Roifman, Ronald Cohn, David Chitayat, Tom H Millard, Nicholas Katsanis, Han G Brunner, Siddharth Banka
RAC1 is a widely studied Rho GTPase, a class of molecules that modulate numerous cellular functions essential for normal development. RAC1 is highly conserved across species and is under strict mutational constraint. We report seven individuals with distinct de novo missense RAC1 mutations and varying degrees of developmental delay, brain malformations, and additional phenotypes. Four individuals, each harboring one of c.53G>A (p.Cys18Tyr), c.116A>G (p.Asn39Ser), c.218C>T (p.Pro73Leu), and c.470G>A (p...
September 7, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28882897/the-tiam1-guanine-nucleotide-exchange-factor-is-auto-inhibited-by-its-pleckstrin-homology-coiled-coil-extension-domain
#11
Zhen Xu, Lokesh Gakhar, Fletcher E Bain, Maria Spies, Ernesto J Fuentes
T-cell lymphoma invasion and metastasis 1 (Tiam1) is a Dbl-family guanine nucleotide exchange factor (GEF) that specifically activates the Rho-family GTPase Rac1 in response to upstream signals, thereby regulating cellular processes including cell adhesion and migration. Tiam1 contains multiple domains, including an N-terminal Pleckstrin homology coiled-coiled extension (PHn-CC-Ex) and catalytic Dbl-homology and C-terminal Pleckstrin homology (DH-PHc) domain. Previous studies indicate that larger fragments of Tiam1, such the region encompassing the N-terminal to C-terminal Pleckstrin homology domains (PHn-PHc) are auto-inhibited...
September 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28880939/arf6-mediates-nephrin-tyrosine-phosphorylation-induced-podocyte-cellular-dynamics
#12
Jamie S Lin, Jin Seok Jeon, Qingfeng Fan, Hetty N Wong, Matthew B Palmer, Lawrence B Holzman
ADP-ribosylation factor 6 (ARF6) is a small GTPase necessary for regulating cellular structure, motility, and vesicle trafficking. In several cellular systems, ARF6 was shown to regulate actin dynamics in coordination with Rac1, a Rho small GTPase. We examined the function of ARF6 in the kidney podocyte because Rac1 was implicated in kidney diseases involving this cell. We found that ARF6 expression was enriched in human podocytes and that it modulated podocyte cytoskeletal dynamics through a functional interaction with nephrin, an intercellular junction protein necessary for podocyte injury-induced signaling requiring activation by tyrosine phosphorylation of its cytoplasmic domain...
2017: PloS One
https://www.readbyqxmd.com/read/28870903/role-of-arhgap24-in-adp-ribosylation-factor-6-arf6-dependent-pseudopod-formation-in-human-breast-carcinoma-cells
#13
Shota Uehara, Koji Saito, Hisayo Asami, Yasutaka Ohta
BACKGROUND/AIM: The small GTPase ADP ribosylation factor 6 (ARF6) promotes carcinoma cell invasion and metastasis through remodeling of actin cytoskeleton and formation of pseudopod that is regulated by RAC. RHO GTPase activating protein 24 (ARHGAP24), a RAC-specific GTPase activating protein, binds to activated ARF6 and is recruited to the plasma membrane. The aim of the present study was to demonstrate if ARHGAP24 is involved in the ARF6-mediated formation of pseudopods in breast carcinoma cells...
September 2017: Anticancer Research
https://www.readbyqxmd.com/read/28860633/a-cdc42-centered-signaling-unit-is-a-dominant-positive-regulator-of-endothelial-integrity
#14
J Amado-Azevedo, N R Reinhard, J van Bezu, R X de Menezes, V W van Beusechem, G P van Nieuw Amerongen, V W M van Hinsbergh, P L Hordijk
Endothelial barrier function is carefully controlled to protect tissues from edema and damage inflicted by extravasated leukocytes. RhoGTPases, in conjunction with myriad regulatory proteins, exert both positive and negative effects on the endothelial barrier integrity. Precise knowledge about the relevant mechanisms is currently fragmented and we therefore performed a comprehensive analysis of endothelial barrier regulation by RhoGTPases and their regulators. Combining RNAi with electrical impedance measurements we quantified the relevance of 270 Rho-associated genes for endothelial barrier function...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28859988/cytoskeletal-remodeling-via-rho-gtpases-during-oxidative-and-thermal-stress-in-caenorhabditis-elegans
#15
Rahul Patel, Sindhu Sriramoji, Marena Marucci, Ibrahim Aziz, Sejal Shah, Federico Sesti
Biological systems are highly sensitive to changes in their environment. Indeed, the molecular basis of the environmental stress response suggests that the specialized stress responses share more commonalities than previously believed. Here, we used the nematode C. elegans to gain insight into the role of Rho signaling during two common environmental challenges, oxidative and thermal stress. In response to heat shock (HS), wild type (N2) worms demonstrated reduced viability which was rescued by genetic suppression of CDC42 and RHO-1...
August 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28852060/fmnl2-and-3-regulate-golgi-architecture-and-anterograde-transport-downstream-of-cdc42
#16
Frieda Kage, Anika Steffen, Adolf Ellinger, Carmen Ranftler, Christian Gehre, Cord Brakebusch, Margit Pavelka, Theresia Stradal, Klemens Rottner
The Rho-family small GTPase Cdc42 localizes at plasma membrane and Golgi complex and aside from protrusion and migration operates in vesicle trafficking, endo- and exocytosis as well as establishment and/or maintenance of cell polarity. The formin family members FMNL2 and -3 are actin assembly factors established to regulate cell edge protrusion during migration and invasion. Here we report these formins to additionally accumulate and function at the Golgi apparatus. As opposed to lamellipodia, Golgi targeting of these proteins required both their N-terminal myristoylation and the interaction with Cdc42...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28851822/protein-kinase-n3-promotes-bone-resorption-by-osteoclasts-in-response-to-wnt5a-ror2-signaling
#17
Shunsuke Uehara, Nobuyuki Udagawa, Hideyuki Mukai, Akihiro Ishihara, Kazuhiro Maeda, Teruhito Yamashita, Kohei Murakami, Michiru Nishita, Takashi Nakamura, Shigeaki Kato, Yasuhiro Minami, Naoyuki Takahashi, Yasuhiro Kobayashi
Cytoskeletal reorganization in osteoclasts to form actin rings is necessary for these cells to attach to bone and resorb bone matrices. We delineated the pathway through which Wnt5a signaling through receptor tyrosine kinase-like orphan receptor 2 (Ror2) promoted the bone-resorbing activity of osteoclasts. Wnt5a binding to Ror2 stimulated Rho, a small GTPase involved in cytoskeletal reorganization. Subsequently, the Rho effector kinase Pkn3 bound to and enhanced the activity of c-Src, a nonreceptor tyrosine kinase that is critical for actin ring formation...
August 29, 2017: Science Signaling
https://www.readbyqxmd.com/read/28844967/cdna-cloning-expression-and-immune-function-analysis-of-a-novel-rac1-gene-ajrac1-in-the-sea-cucumber-apostichopus-japonicus
#18
Kaiquan Li, Lin Liu, Shengnan Shang, Yi Wang, Yaoyao Zhan, Jian Song, Xiangxiang Zhang, Yaqing Chang
The ras-related C3 botulinum toxin substrate 1 (Rac1) belongs to Ras homolog (Rho) small GTPases subfamily. As an important molecular switch, Rac1 regulates various processes in the cell, especially in cellular immune response. With attempt to clarify characters and functions of Rac1 in sea cucumbers, full length cDNA of a Rac1 homolog in the sea cucumber Apostichopus japonicus (AjRac1) was cloned by transcriptome database mining and rapid amplification of cDNA ends (RACE) techniques. The open reading frame of AjRac1 is 579 bp encoding a protein with a length of 192 aa...
August 26, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28842497/the-binding-of-activated-g%C3%AE-q-to-phospholipase-c-%C3%AE-exhibits-anomalous-affinity
#19
Punya Navaratnarajah, Anne Gershenson, Elliott M Ross
Upon activation by the Gq family of Gα subunits, Gβγ subunits and some Rho family GTPases, phospholipase C-β (PLC-β) isoforms hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP2) to the second messengers inositol 1,4,5-trisphosphate and diacylglycerol. PLC-β isoforms also function as GTPase-activating proteins (GAPs), potentiating Gq deactivation. To elucidate the mechanism of this mutual regulation, we measured the thermodynamics and kinetics of PLC-β3 binding to Gαq. Fluorescence resonance energy transfer (FRET) and fluorescence correlation spectroscopy, two physically distinct methods, both yielded Kd values of about 200 nM for PLC-β3-Gαq binding...
August 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28842414/the-atypical-map-kinase-swip-13-erk8-regulates-dopamine-transporters-through-a-rho-dependent-mechanism
#20
Daniel P Bermingham, J Andrew Hardaway, Osama Refai, Christian R Marks, Sam L Snider, Sarah M Sturgeon, William C Spencer, Roger J Colbran, David M Miller, Randy D Blakely
The neurotransmitter dopamine (DA) regulates multiple behaviors across phylogeny, with disrupted DA signaling in humans associated with addiction, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and Parkinson's disease. The DA transporter (DAT) imposes spatial and temporal limits on DA action, and provides for presynaptic DA recycling to replenish neurotransmitter pools. Molecular mechanisms that regulate DAT expression, trafficking and function, particularly in vivo, remain poorly understood, though recent studies have implicated Rho-linked pathways in psychostimulant action...
August 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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