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Small GTPases

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https://www.readbyqxmd.com/read/29772958/arf6-and-rab11-as-intrinsic-regulators-of-axon-regeneration
#1
Bart Nieuwenhuis, Richard Eva
Adult central nervous system (CNS) axons do not regenerate after injury because of extrinsic inhibitory factors, and a low intrinsic capacity for axon growth. Developing CNS neurons have a better regenerative ability, but lose this with maturity. This mini-review summarises recent findings which suggest one reason for regenerative failure is the selective distribution of growth machinery away from axons as CNS neurons mature. These studies demonstrate roles for the small GTPases ARF6 and Rab11 as intrinsic regulators of polarised transport and axon regeneration...
May 17, 2018: Small GTPases
https://www.readbyqxmd.com/read/29733762/filling-gaps-in-g-protein-coupled-receptor-gpcr-mediated-ras-adaptation-and-chemotaxis
#2
Xu Xuehua
Eukaryotic cells sense and migrate toward chemoattractant gradients using G protein-coupled receptor (GPCR) signaling pathways. The fascinating feature of chemotaxis is that cells migrate through chemoattractant gradients with huge concentration ranges by "adaptation." Adaptive cells no longer respond to the present stimulus but remain sensitive to stronger stimuli, providing the fundamental strategy for chemotaxis through gradients with a broad range of concentrations. Ras activation is the first step in the GPCR-mediated chemosensing signaling pathways that displays adaptation...
May 7, 2018: Small GTPases
https://www.readbyqxmd.com/read/29457552/reciprocal-regulation-of-yap-taz-by-the-hippo-pathway-and-the-small-gtpase-pathway
#3
Ju-Won Jang, Min-Kyu Kim, Suk-Chul Bae
Yes-associated protein 1 (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) (YAP/TAZ) are transcriptional coactivators that regulate genes involved in proliferation and transformation by interacting with DNA-binding transcription factors. Remarkably, YAP/TAZ are essential for cancer initiation or growth of most solid tumors. Their activation induces cancer stem cell attributes, proliferation, and metastasis. The oncogenic activity of YAP/TAZ is inhibited by the Hippo cascade, an evolutionarily conserved pathway that is governed by two kinases, mammalian Ste20-like kinases 1/2 (MST1/2) and Large tumor suppressor kinase 1/2 (LATS1/2), corresponding to Drosophila's Hippo (Hpo) and Warts (Wts), respectively...
April 20, 2018: Small GTPases
https://www.readbyqxmd.com/read/29634387/-examining-ras-pathway-rewiring-with-a-chemically-inducible-activator-of-ras
#4
John C Rose, Emily M Dieter, Daniel Cunningham-Bryant, Dustin J Maly
RAS signaling pathways govern diverse cellular processes, are dynamic, and exhibit marked plasticity. Yet, these features also present a considerable obstacle to their study. Here, we report the use of a recently described RAS rheostat, Chemically Inducible Activator of RAS (CIAR), to study two poorly understood phenomena in RAS biology. First, we show that short-term activation of wild type endogenous RAS can desensitize cells to EGF stimulation. Second, we examine the phenomena of paradoxical activation of RAS/ERK signaling by RAF inhibitors...
April 10, 2018: Small GTPases
https://www.readbyqxmd.com/read/29457531/shedding-new-light-on-rhoa-signalling-as-a-drug-target-in-vivo-using-a-novel-rhoa-fret-biosensor-mouse
#5
Max Nobis, David Herrmann, Sean C Warren, Douglas Strathdee, Thomas R Cox, Kurt I Anderson, Paul Timpson
The small GTPase RhoA is a master regulator of signalling in cell-extracellular matrix interactions. RhoA signalling is critical to many cellular processes including migration, mechanotransduction, and is often disrupted in carcinogenesis. Investigating RhoA activity in a native tissue environment is challenging using conventional biochemical methods; we therefore developed a RhoA-FRET biosensor mouse, employing the adaptable nature of intravital imaging to a variety of settings. Mechanotransduction was explored in the context of osteocyte processes embedded in the calvaria responding in a directional manner to compression stress...
March 21, 2018: Small GTPases
https://www.readbyqxmd.com/read/29099310/rab-proteins-as-major-determinants-of-the-golgi-complex-structure
#6
Bruno Goud, Shijie Liu, Brian Storrie
GTP-ases of the Rab family (about 70 in human) are key regulators of intracellular transport and membrane trafficking in eukaryotic cells. Remarkably, almost one third associate with membranes of the Golgi complex and TGN (trans-Golgi network). Through interactions with a variety of effectors that include molecular motors, tethering complexes, scaffolding proteins and lipid kinases, they play an important role in maintaining Golgi architecture.
March 4, 2018: Small GTPases
https://www.readbyqxmd.com/read/28426288/post-translational-modifications-of-rab-gtpases
#7
Swapnil Rohidas Shinde, Subbareddy Maddika
Rab GTPases, the highly conserved members of Ras GTPase superfamily are central players in the vesicular trafficking. They are critically involved in intracellular trafficking pathway, beginning from formation of vesicles on donor membranes, defining trafficking specificity to facilitating vesicle docking on target membranes. Given the dynamic roles of Rabs during different stages of vesicular trafficking, mechanisms for their spatial and temporal regulation are crucial for normal cellular function. Regulation of Rab GTPase activity, localization and function has always been focused in and around the association of GDP dissociation inhibitor (GDI), Guanine nucleotide Exchange Factor (GEFs) and GTPase accelerating protein (GAP) to Rabs...
March 4, 2018: Small GTPases
https://www.readbyqxmd.com/read/28135905/new-insights-into-the-function-of-rab-gtpases-in-the-context-of-exosomal-secretion
#8
Lionel Blanc, Michel Vidal
In the last two decades, extracellular vesicle-mediated communication between cells has become a major field in cell biology. However, the function of extracellular vesicles is far from clear, especially due to the disparity of released vesicles by cells. Basically, one must consider vesicles budding from the cell plasma membrane (ectosomes) and vesicles released upon fusion of an endosomal multivesicular compartment (exosomes). Moreover, even for exosomes, we report and discuss here the possibility that different routes regulated by specific Rab GTPases might produce exosomes having various biologic functions...
March 4, 2018: Small GTPases
https://www.readbyqxmd.com/read/29457987/the-rap2c-gtpase-facilitates-b-cell-receptor-induced-reorientation-of-the-microtubule-organizing-center
#9
Jia C Wang, Jeff Y-J Lee, May Dang-Lawson, Caitlin Pritchard, Michael R Gold
When B lymphocytes encounter antigen-bearing surfaces, B-cell receptor (BCR) signaling initiates remodeling of the F-actin network and reorientation of the microtubule-organizing center (MTOC) towards the antigen contact site. We have previously shown that the Rap1 GTPase, an evolutionarily conserved regulator of cell polarity, is essential for these processes and that Rap1-regulated actin remodeling is required for MTOC polarization. The role of Rap2 proteins in establishing cell polarity is not well understood...
February 19, 2018: Small GTPases
https://www.readbyqxmd.com/read/29455593/acute-compressive-stress-activates-rho-rock-mediated-cellular-processes
#10
Sarah T Boyle, Jasreen Kular, Max Nobis, Andrew Ruszkiewicz, Paul Timpson, Michael S Samuel
The ability to rapidly respond to applied force underpins cell/tissue homeostasis. This response is mediated by mechanotransduction pathways that regulate remodeling and tension of the actomyosin cytoskeleton to counterbalance external forces. Enhanced extracellular matrix tension hyper-activates mechanotransduction and characterizes diseased states such as cancer, but is also required for normal epidermal regeneration. While the impact of extracellular matrix tension on signaling and cell biology are well appreciated, that of acute compressive force is under-studied...
February 17, 2018: Small GTPases
https://www.readbyqxmd.com/read/29388865/multiple-rap1-effectors-control-epac1-mediated-tightening-of-endothelial-junctions
#11
Willem-Jan Pannekoek, Marjolein J Vliem, Johannes L Bos
Epac1 and Rap1 mediate cAMP-induced tightening of endothelial junctions. We have previously found that one of the mechanisms is the inhibition of Rho-mediated tension in radial stress fibers by recruiting the RhoGAP ArhGAP29 in a complex containing the Rap1 effectors Rasip1 and Radil. However, other mechanisms have been proposed as well, most notably the induction of tension in circumferential actin cables by Cdc42 and its GEF FGD5. Here, we have investigated how Rap1 controls FGD5/Cdc42 and how this interconnects with Radil/Rasip1/ArhGAP29...
February 17, 2018: Small GTPases
https://www.readbyqxmd.com/read/29172947/crosstalk-between-wip-and-rho-family-gtpases
#12
Inés M Antón, Carla Gómez-Oro, Sergio Rivas, Francisco Wandosell
Through actin-binding proteins such as the neural Wiskott-Aldrich syndrome protein (N-WASP) and WASP-interacting protein (WIP), the Rho family GTPases RhoA, Rac1 and Cdc42 are major modulators of the cytoskeleton. (N-)WASP and WIP control Rho GTPase activity in various cell types, either by direct WIP/(N-)WASP/Cdc42 or potential WIP/RhoA binding, or through secondary links that regulate GTPase distribution and/or transcription levels. WIP helps to regulate filopodium generation and participates in the Rac1-mediated ruffle formation that determines cell motility...
January 29, 2018: Small GTPases
https://www.readbyqxmd.com/read/29157138/fast-cycling-rho-gtpases
#13
Pontus Aspenström
The Rho GTPases were discovered more than 30 years ago, and they were for a long time considered to follow simple cycling between GDP-bound and GTP-bound conformations, as for the Ras subfamily of small GTPases. The Rho GTPases consist of 20 members, but at least 10 of these do not follow this classical GTPase cycle. Thus, based on their kinetic properties, these Rho GTPases can instead be classified as atypical. Some of these atypical Rho GTPases do not hydrolyze GTP, and some have significantly increased intrinsic GDP/GTP exchange activity...
January 29, 2018: Small GTPases
https://www.readbyqxmd.com/read/29368995/rab-gtpases-master-controllers-of-eukaryotic-trafficking
#14
Jean Claude Hervé, Nicolas Bourmeyster
No abstract text is available yet for this article.
January 25, 2018: Small GTPases
https://www.readbyqxmd.com/read/29261009/small-change-big-effect-taking-ras-by-the-tail-through-suppression-of-post-prenylation-carboxylmethylation
#15
Hiu Yeung Lau, Mei Wang
Mutant RAS isoforms are the most common oncogenes affecting human cancers. After decades of effort in developing drugs targeting oncogenic RAS-driven cancers, we are still charting an unclear path. Despite recent developments exemplified by KRAS (G12C) inhibitors, direct targeting of mutant RAS remains a difficult endeavor. Inhibiting RAS function by targeting its post-translational prenylation processing has remained an important approach, especially with recent progress on the study of isoprenylcysteine carboxylmethyltransferase (ICMT), the unique enzyme for the last step of prenylation processing of RAS isoforms and other substrates...
January 25, 2018: Small GTPases
https://www.readbyqxmd.com/read/29363391/brag1-iqsec2-as-a-regulator-of-small-gtpase-dependent-trafficking
#16
Amber Petersen, Joshua C Brown, Nashaat Z Gerges
Precise trafficking events, such as those that underlie synaptic transmission and plasticity, require complex regulation. G-protein signaling plays an essential role in the regulation of membrane and protein trafficking. However, it is not well understood how small GTPases and their regulatory proteins coordinate such specific events. Our recent publication focused on a highly abundant synaptic GEF, BRAG1, whose physiologic relevance was unknown. We find that BRAG1s GEF activity is required for activity-dependent trafficking of AMPARs...
January 24, 2018: Small GTPases
https://www.readbyqxmd.com/read/29313423/rho-guanosine-nucleotide-exchange-factors-are-not-such-bad-guys-after-all-in-cancer-a
#17
Javier Robles-Valero, L Francisco Lorenzo-Martín, Isabel Fernández-Pisonero, Xosé R Bustelo
Rho GDP/GTP exchange factors (GEFs), the enzymes that trigger the stimulation of Rho GTPases during cell signaling, are widely deemed as potential therapeutic targets owing to their protumorigenic functions. However, the sparse use of animal models has precluded a full understanding of their pathophysiological roles at the organismal level. In a recent article in Cancer Cell, we have reported that the Vav1 GEF unexpectedly acts as a tumor suppressor by mediating the noncatalytic nucleation of cytoplasmic complexes between the E3 ubiquitin ligase Cbl-b and the active Notch1 intracellular domain (ICN1)...
January 24, 2018: Small GTPases
https://www.readbyqxmd.com/read/29239694/a-novel-prenyl-polybasic-domain-code-determines-lipid-binding-specificity-of-the-k-ras-membrane-anchor
#18
Yong Zhou, John F Hancock
Ras proteins must localize to the plasma membrane (PM) for biological function. The membrane anchor of the K-Ras4B isoform comprises a farnesylated and methylated C-terminal cysteine together with an adjacent hexa-lysine polybasic domain (PBD). Traditionally, polybasic sequences have been thought to interact electrostatically with negatively charged membranes showing no specificity for anionic lipid head groups. By contrast we recently showed that the K-Ras membrane anchor actually exhibits a very high degree of specificity for phosphatidylserine (PtdSer)...
January 15, 2018: Small GTPases
https://www.readbyqxmd.com/read/29261068/expression-of-a-t39n-mutant-rab32-protein-arrests-mitochondria-movement-within-neurites-of-differentiated-sh-sy5y-cells
#19
Jonas Rybnicek, Samira Samtleben, Maria Sol Herrera-Cruz, Thomas Simmen
We have shown that multiple sclerosis (MS) and endoplasmic reticulum (ER) stress induce Rab32, an ER/mitochondria-localized small GTPase. High levels of both dominant-active (Q85L) or dominant-inactive (T39N) Rab32 are toxic to neurons. While Rab32Q85L interacts with its effector Drp1 to promote mitochondria fission, it is unclear how Rab32T39N could result as toxic to neurons. Given the perinuclear clustering of mitochondria observed upon transfection of inactive Rab32, we hypothesized Rab32T39N could stall mitochondria within neurites...
January 7, 2018: Small GTPases
https://www.readbyqxmd.com/read/29173049/light-directed-migration-of-a-cluster-of-cells-in-the-centimeter-scale
#20
Abdullah Al Mosabbir, Kevin Truong
Protein-based systems for light directed migration of cells have been demonstrated up to distances of several hundred microns, but larger distances in the centimeter scale would allow new possible applications. Light activated migration in mammalian cells can be achieved by cells expressing channelrhodopsin-2 and an engineered Ca2+ sensitive Rac1 protein called RACer. In this study, light was used to induce wound healing, localize cells into a region of interest, and move cells over centimeter scale distances...
January 7, 2018: Small GTPases
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