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Small GTPases

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https://www.readbyqxmd.com/read/29457987/the-rap2c-gtpase-facilitates-b-cell-receptor-induced-reorientation-of-the-microtubule-organizing-center
#1
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/29457552/reciprocal-regulation-of-yap-taz-by-the-hippo-pathway-and-the-small-gtpase-pathway
#2
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...
February 18, 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
#3
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. Mechnotransduction was explored in the context of osteocyte processes embedded in the calvaria responding in a directional manner to compression stress...
February 18, 2018: Small GTPases
https://www.readbyqxmd.com/read/29455593/acute-compressive-stress-activates-rho-rock-mediated-cellular-processes
#4
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
#5
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 1, 2018: Small GTPases
https://www.readbyqxmd.com/read/29368995/rab-gtpases-master-controllers-of-eukaryotic-trafficking
#6
Jean Claude Hervé, Nicolas Bourmeyster
No abstract text is available yet for this article.
January 25, 2018: Small GTPases
https://www.readbyqxmd.com/read/29363391/brag1-iqsec2-as-a-regulator-of-small-gtpase-dependent-trafficking
#7
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-cancera
#8
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 9, 2018: Small GTPases
https://www.readbyqxmd.com/read/29291271/shared-mechanisms-regulate-spatiotemporal-rhoa-dependent-actomyosin-contractility-during-adhesion-and-cell-division
#9
Patrick W B Derksen, Robert A H van de Ven
Local modulation of the actin cytoskeleton is essential for the initiation and maintenance of strong homotypic adhesive interfaces between neighboring cells. The epithelial adherens junction (AJ) fulfils a central role in this process by mediating E-cadherin interactions and functioning as a signaling scaffold to control the activity of the small GTPase RhoA and subsequent actomyosin contractility. Interestingly, a number of regulatory proteins that modulate RhoA activity at the AJ also control RhoA during cytokinesis, an actomyosin-dependent process that divides the cytoplasm to generate two daughter cells at the final stages of mitosis...
December 31, 2017: Small GTPases
https://www.readbyqxmd.com/read/29284321/ral-function-in-muscle-is-required-for-flight-maintenance-in-drosophila
#10
Shlesha Richhariya, Gaiti Hasan
Ral is a small GTPase of the Ras superfamily that is important for a number of cellular functions. Recently, we found that expression of Ral is regulated by store-operated calcium entry (SOCE) in Drosophila neurons. In this study, through genetic and behavioural experiments, we show that Ral function is required in differentiated muscles for flight. Reducing Ral function in muscles, specifically reduced duration of flight bouts but not other motor functions, like climbing. Interestingly, unlike in the nervous system, Ral expression in the muscle is not regulated by SOCE...
December 28, 2017: 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
#11
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...
December 20, 2017: Small GTPases
https://www.readbyqxmd.com/read/29261009/small-change-big-effect-taking-ras-by-the-tail-through-suppression-of-post-prenylation-carboxylmethylation
#12
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...
December 20, 2017: Small GTPases
https://www.readbyqxmd.com/read/29239694/a-novel-prenyl-polybasic-domain-code-determines-lipid-binding-specificity-of-the-k-ras-membrane-anchor
#13
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)...
December 14, 2017: Small GTPases
https://www.readbyqxmd.com/read/29239692/consequences-of-rab-gtpase-dysfunction-in-genetic-or-acquired-human-diseases
#14
Marcellus J Banworth, Guangpu Li
Rab GTPases are important regulators of intracellular membrane trafficking in eukaryotes. Both activating and inactivating mutations in Rab genes have been identified and implicated in human diseases ranging from neurological disorders to cancer. In addition, altered Rab expression is often associated with disease prognosis. As such, the study of diseases associated with Rabs or Rab-interacting proteins has shed light on the important role of intracellular membrane trafficking in disease etiology. In this review, we cover recent advances in the field with an emphasis on cellular mechanisms...
December 14, 2017: Small GTPases
https://www.readbyqxmd.com/read/29199510/regulation-of-rhoa-gtpase-and-novel-target-proteins-for-rock
#15
Eun-Kyoung Choi, Jae-Gyu Kim, Hee-Jun Kim, Jung-Yoon Cho, Hwalrim Jeong, Yohan Park, Rokibul Islam, Cuong Kim Cap, Jae-Bong Park
Rho GTPases play significant roles in cellular function and their activity is regulated by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), providing activation and inactivation of these GTPases, respectively. Active GTP-bound form of RhoA activates its effector proteins while the inactive GDP-bound form of RhoA exists in a RhoA-RhoGDI (guanine nucleotide dissociation inhibitor) complex in the cytosol. In particular, IκB kinase γ IKKγ/NF-κB essential modulator (NEMO) plays a role as a GDI displacement factor (GDF) for RhoA activation through binding to RhoA-RhoGDI complex...
December 3, 2017: Small GTPases
https://www.readbyqxmd.com/read/29189096/regulation-and-functions-of-rhou-and-rhov
#16
Richard G Hodge, Anne J Ridley
Rho GTPases play central roles in a wide variety of cellular processes, including cytoskeletal dynamics, cell adhesion and cell polarity. RhoU and RhoV are Rho GTPases that have some atypical properties compared with classical Rho family members, such as the presence of N- and C-terminal extension regions, unusual GDP/GTP cycling and post-translational modification by palmitoylation but not prenylation. Their activity and localization is regulated by the N-terminal and C-terminal regions, and so far no GEFs or GAPs have been identified for them...
November 30, 2017: Small GTPases
https://www.readbyqxmd.com/read/29188751/go-with-the-flow-gef-h1-mediated-shear-stress-mechanotransduction-in-neutrophils
#17
Noah Fine, Ioannis D Dimitriou, Robert Rottapel
Neutrophils in circulation experience significant shear forces due to blood flow when they tether to the vascular endothelium. Biochemical and biophysical responses of neutrophils to the physical force of flowing blood modulate their behavior and promote tissue recruitment under pro-inflammatory conditions. Neutrophil mechanotransduction responses occur through mechanisms that are not yet fully understood. In our recent work, we showed that GEF-H1, a RhoA specific guanine nucleotide exchange factor (GEF), is required to maintain neutrophil motility and migration in response to shear stress...
November 30, 2017: Small GTPases
https://www.readbyqxmd.com/read/29185861/of-rings-and-spines-the-multiple-facets-of-citron-proteins-in-neural-development
#18
Federico T Bianchi, Marta Gai, Gaia E Berto, Ferdinando Di Cunto
The Citron protein was originally identified for its capability to specifically bind the active form of RhoA small GTPase, leading to the simplistic hypothesis that it may work as a RhoA downstream effector in actin remodeling. More than two decades later, a much more complex picture has emerged. In particular, it has become clear that in animals, and especially in mammals, the functions of the Citron gene (CIT) are intimately linked to many aspects of central nervous system (CNS) development and function, although the gene is broadly expressed...
November 29, 2017: Small GTPases
https://www.readbyqxmd.com/read/29185849/ras-ubiquitylation-modulates-effector-interactions
#19
Ryan Thurman, Edhriz Siraliev-Perez, Sharon L Campbell
RAS proteins function as molecular switches that regulate cellular growth by cycling between active GTP- and inactive GDP bound states. While RAS activity is modulated by factors (guanine nucleotide exchange and GTPase activating proteins) that control levels of active Ras-GTP, RAS proteins also undergo a number of post-translational modifications that regulate their function. One such modification is ubiquitylation. Monoubiquitylation of KRAS at lysine 147 (mUbRAS) enhances Ras activation and promotes signaling through the RAF and Phosphoinositide 3-Kinase (PI3K) signaling pathways...
November 29, 2017: 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...
November 26, 2017: Small GTPases
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