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Small GTPases

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https://www.readbyqxmd.com/read/30043672/small-gtpase-ras-in-multiple-sclerosis-exploring-the-role-of-ras-gtpase-in-the-etiology-of-multiple-sclerosis
#1
Samantha Messina
RAS signaling is involved in the development of autoimmunity in general. Multiple sclerosis (MS) is a T cell-mediated autoimmune disease of the central nervous system. It is widely recognized that a reduction of Foxp3+ regulatory T (Treg) cells is an immunological hallmark of MS, but the underlying mechanisms are unclear. In experimental autoimmune models, N-Ras and K-Ras inhibition triggers an anti-inflammatory effect up-regulating, via foxp3 elevation, the numbers and the functional suppressive properties of Tregs...
September 18, 2018: Small GTPases
https://www.readbyqxmd.com/read/30182785/increasing-spatial-resolution-of-photoregulated-gtpases-through-immobilized-peripheral-membrane-proteins
#2
Orry Van Geel, Roland Hartsuiker, Theodorus W J Gadella
Light-induced dimerizing systems, e.g. iLID, are an increasingly utilized optogenetics tool to perturb cellular signaling. The major benefit of this technique is that it allows external spatiotemporal control over protein localization with sub-cellular specificity. However, when it comes to local recruitment of signaling components to the plasmamembrane, this precision in localization is easily lost due to rapid diffusion of the membrane anchor. In this study, we explore different approaches of countering the diffusion of peripheral membrane anchors, to the point where we detect immobilized fractions with iFRAP on a timescale of several minutes...
September 5, 2018: Small GTPases
https://www.readbyqxmd.com/read/30156960/the-rab7-subfamily-across-paramecium-aurelia-species-evidence-of-high-conservation-in-sequence-and-function
#3
Lydia J Bright, Michael Lynch
We examined sequence conservation and signatures of selection in Rab7 proteins across 11 Paramecium aurelia species, and determined the localization patterns of two P. tetraurelia Rab7 paralogs when expressed as GFP fusions in live cells. We found that, while there is a variable number of Rab7 paralogs per genome, Rab7 genes are highly conserved in sequence and appear to be under strong purifying selection across aurelias. Additionally, and surprisingly based on earlier studies, we found that two P. tetraurelia Rab7 proteins have virtually identical localization patterns...
August 29, 2018: Small GTPases
https://www.readbyqxmd.com/read/30032715/a-potential-rho-gef-and-rac-gap-for-coupled-rac-and-rho-cycles-during-mesenchymal-to-epithelial-like-transitions
#4
Christopher P Toret, Andre Le Bivic
The leading edge-to-cadherin contact transitions that occur during metazoan developmental processes and disease states require fine coordination of Rac and Rho pathways. Recently the elmo-mbc complex, a Rac GEF and RhoGAP19D, a Rho GAP were identified as key, conserved regulators that link Rac and Rho during these transitions. The corresponding Rho GEF and Rac GAP remain hidden amongst the large family of GEF and GAP proteins. Identification of these regulators is essential to understand GTPase coordination during these transitions...
August 29, 2018: Small GTPases
https://www.readbyqxmd.com/read/29969362/targeting-cdc42-with-the-anticancer-compound-mbq-167-inhibits-cell-polarity-and-growth-in-the-budding-yeast-s-cerevisiae
#5
Michael John Rivera-Robles, Julia Medina-Velázquez, Gabriela M Asencio-Torres, Sahily González-Crespo, Brian C Rymond, José Rodríguez-Medina, Suranganie Dharmawardhane
The Rho GTPase Cdc42 is highly conserved in structure and function. Mechanical or chemical cues in the microenvironment stimulate the localized activation of Cdc42 to rearrange the actin cytoskeleton and establish cell polarity. A role for Cdc42 in cell polarization was first discovered in the budding yeast Saccharomyces cerevisiae, and subsequently shown to also regulate directional motility in animal cells. Accordingly, in cancer Cdc42 promotes migration, invasion, and spread of tumor cells. Therefore, we targeted Cdc42 as a therapeutic strategy to treat metastatic breast cancer and designed the small molecule MBQ-167 as a potent inhibitor against Cdc42 and the homolog Rac...
July 29, 2018: Small GTPases
https://www.readbyqxmd.com/read/27880081/an-emerging-role-for-iqgap1-in-tight-junction-control
#6
Barbara E Tanos, Charles Yeaman, Enrique Rodriguez-Boulan
IQGAP1 is a scaffold protein involved in the assembly of adherens junctions. Our work has recently revealed a novel role for IQGAP1 in the regulation of tight junctions (TJ) through differential recruitment of claudins to the nascent TJ. Here, we discuss the potential mechanisms of this regulation, including IQGAP1 effects on CDC42, and IQGAP1 interactions with sorting/trafficking molecules (e.g. Exo70). Given the many roles of IQGAP1 and the large number of interacting partners, we focus our discussion of these functions in the context of junction formation, trafficking, growth factor signaling and cancer...
September 3, 2018: Small GTPases
https://www.readbyqxmd.com/read/27875099/the-rhob-small-gtpase-in-physiology-and-disease
#7
Francisco M Vega, Anne J Ridley
RhoB is a Rho family GTPase that is highly similar to RhoA and RhoC, yet has distinct functions in cells. Its unique C-terminal region is subject to specific post-translational modifications that confer different localization and functions to RhoB. Apart from the common role with RhoA and RhoC in actin organization and cell migration, RhoB is also implicated in a variety of other cellular processes including membrane trafficking, cell proliferation, DNA-repair and apoptosis. RhoB is not an essential gene in mice, but it is implicated in several physiological and pathological processes...
September 3, 2018: Small GTPases
https://www.readbyqxmd.com/read/27854154/small-gtpases-in-c-elegans-metabolism
#8
Daniel Z Bar, Chayki Charar, Yosef Gruenbaum
The mechanistic target of rapamycin (mTOR) is an evolutionary conserved protein with a serine/threonine kinase activity that regulates cell growth, proliferation, motility, survival, protein synthesis, autophagy and transcription. It is embedded in 2 large protein complexes: mTORC1 and mTORC2. Regulation of specific mTOR pathway functions depends on multiple GTPases, that act either as regulators of mTOR protein complexes, coupling energy availability with mTORC1 activity, or as downstream effectors of both mTORC1 and mTORC2...
September 3, 2018: Small GTPases
https://www.readbyqxmd.com/read/27768524/c9orf72-plays-a-central-role-in-rab-gtpase-dependent-regulation-of-autophagy
#9
Christopher P Webster, Emma F Smith, Andrew J Grierson, Kurt J De Vos
A GGGGCC hexanucleotide repeat expansion in the first intron of the C9orf72 gene is the most common genetic defect associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9ALS/FTD). Haploinsufficiency and a resulting loss of C9orf72 protein function has been suggested as a possible pathogenic mechanism in C9ALS/FTD. C9ALS/FTD patients exhibit specific ubiquitin and p62/sequestosome-1 positive but TDP-43 negative inclusions in the cerebellum and hippocampus, indicating possible autophagy deficits in these patients...
September 3, 2018: Small GTPases
https://www.readbyqxmd.com/read/27763815/diverted-recycling-shigella-subversion-of-rabs
#10
Noelia López-Montero, Jost Enninga
Small GTPases of the Rab protein family control intracellular vesicular trafficking to allow their communication and maintenance. It is a common strategy for intracellular bacteria to exploit these pathways to shape their respective niches for survival. The subversion of Rabs for the generation of an intracellular environment favoring the pathogen has been described almost exclusively for intracellular bacteria that reside within bacterial containing vacuoles (BCVs). However, less is known about Rab subversion for bacteria that rupture the BCV to reach the host cytoplasm...
September 3, 2018: Small GTPases
https://www.readbyqxmd.com/read/27763811/small-gtpase-proteins-in-macroautophagy
#11
Shu Yang, Anne Rosenwald
Macroautophagy, a highly conserved process in eukaryotic cells, is initiated in response to stress, especially nutrient starvation. Macroautophagy helps cells survive by engulfing proteins and organelles into an unusual double-membraned structure called the autophagosome, which then fuses with the lysosome. Upon degradation of the engulfed contents, the building blocks are recycled for synthesis of new macromolecules. Recent work has demonstrated that construction of the autophagosome requires a variety of small GTPases in variations of their normal roles in membrane traffic...
September 3, 2018: Small GTPases
https://www.readbyqxmd.com/read/27754752/rhoa-controls-retinoid-signaling-by-rock-dependent-regulation-of-retinol-metabolism
#12
Alberto García-Mariscal, Karine Peyrollier, Astrid Basse, Esben Pedersen, Ralph Rühl, Jolanda van Hengel, Cord Brakebusch
The ubiquitously expressed small GTPase RhoA is essential for embryonic development and mutated in different cancers. Functionally, it is well described as a regulator of the actin cytoskeleton, but its role in gene regulation is less understood. Using primary mouse keratinocytes with a deletion of the RhoA gene, we have now been exploring how the loss of RhoA affects gene expression. Performing transcription factor reporter assays, we found a significantly decreased activity of a RAR luciferase reporter in RhoA-null keratinocytes...
September 3, 2018: Small GTPases
https://www.readbyqxmd.com/read/27754746/the-distinct-traits-of-extracellular-vesicles-generated-by-transformed-cells
#13
Marc A Antonyak, Richard A Cerione
Intercellular communication mediated by extracellular vesicles (EVs), membrane-enclosed packages released by cells, plays important roles in several physiological and pathological settings. Moreover, EVs have been shown to contain molecular signatures that reflect their cell of origin, raising the possibility that EV cargo could potentially be used to diagnose disease. However, for this to occur, a better understanding of the differences between EVs generated by normal and diseased cells is needed. We recently discovered that the content and function of one major class of EVs, microvesicles (MVs), changes upon the induction of oncogenic transformation...
September 3, 2018: Small GTPases
https://www.readbyqxmd.com/read/27754741/arf6-and-its-zeb1-epb41l5-mesenchymal-axis-are-required-for-both-mesenchymal-and-amoeboid-type-invasion-of-cancer-cells
#14
Haruka Handa, Ari Hashimoto, Shigeru Hashimoto, Hisataka Sabe
Modes of cancer invasion interchange between the mesenchymal type and amoeboid type in response to the microenvironment, in which RhoA and Rac1 are selectively required to perform different modes of actin-cytoskeletal remodeling. Membrane remodeling is another integral part of invasion. Arf6 regulates the recycling of molecules at the cell periphery, and is often overexpressed in malignant cancers together with its effector AMAP1/ASAP1/DDEF1. This pathway promotes mesenchymal-type invasion when AMAP1 binds to EPB41L5, a mesenchymal-specific protein induced by ZEB1...
September 3, 2018: Small GTPases
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...
September 3, 2018: Small GTPases
https://www.readbyqxmd.com/read/28060560/harnessing-membrane-trafficking-to-promote-cancer-spreading-and-invasion-the-case-of-rab2a
#16
Hiroaki Kajiho, Yuko Kajiho, Giorgio Scita
How cancer disseminates and metastasizes remains an outstanding open question. Emerging evidence indicates that membrane trafficking is frequently harnessed by tumors of epithelial origin to acquire a mesenchymal program of invasiveness. However, the critical molecular hubs used by cancer cells this context have only began to be elucidated. Here, we discussed the results of a recent phenotypic screening that led to the identification of the small GTPase RAB2A, not previously involved in cancer dissemination, as pivotal for the acquisition of pericellular proteolysis, cell dissemination and distant metastatic spreading of human breast cancer...
July 4, 2018: Small GTPases
https://www.readbyqxmd.com/read/27768516/rho-gtpases-in-mammalian-spinal-neural-tube-closure
#17
Ana Rolo, Sarah Escuin, Nicholas D E Greene, Andrew J Copp
Neural tube closure is an important morphogenetic event that involves dramatic reshaping of both neural and non-neural tissues. Rho GTPases are key cytoskeletal regulators involved in cell motility and in several developmental processes, and are thus expected to play pivotal roles in neurulation. Here, we discuss 2 recent studies that shed light on the roles of distinct Rho GTPases in different tissues during neurulation. RhoA plays an essential role in regulating actomyosin dynamics in the neural epithelium of the elevating neural folds, while Rac1 is required for the formation of cell protrusions in the non-neural surface ectoderm during neural fold fusion...
July 4, 2018: Small GTPases
https://www.readbyqxmd.com/read/27715492/connecting-g-protein-signaling-to-chemoattractant-mediated-cell-polarity-and-cytoskeletal-reorganization
#18
Youtao Liu, Jesus Lacal, Richard A Firtel, Arjan Kortholt
The directional movement toward extracellular chemical gradients, a process called chemotaxis, is an important property of cells. Central to eukaryotic chemotaxis is the molecular mechanism by which chemoattractant-mediated activation of G-protein coupled receptors (GPCRs) induces symmetry breaking in the activated downstream signaling pathways. Studies with mainly Dictyostelium and mammalian neutrophils as experimental systems have shown that chemotaxis is mediated by a complex network of signaling pathways...
July 4, 2018: Small GTPases
https://www.readbyqxmd.com/read/27687567/nuf-and-rip11-requirement-for-polarity-determinant-recycling-during-drosophila-development
#19
Francisco J Calero-Cuenca, Sol Sotillos
A tight relationship between apico-basal polarity and trafficking is essential for epithelial physiology and tissue homeostasis. Recent studies have described how some Rab GTPases, key components of the intracellular traffic machinery, contribute to the establishment of cell polarity in vertebrates. We have demonstrated a novel connection between cell polarity and trafficking: in Drosophila epithelia, the apical determinant aPKC is recycled via Rab11-Nuf-recycling endosomes to maintain cell polarity. Furthermore, the phosphorylation of Nuf by aPKC allows aPKC to control the sub-cellular localization of Nuf and its own membrane accumulation...
July 4, 2018: Small GTPases
https://www.readbyqxmd.com/read/27687479/rab3a-and-rab10-are-regulators-of-lysosome-exocytosis-and-plasma-membrane-repair
#20
Otilia V Vieira
Disruption of the cell plasma membrane can occur due to mechanical damage, pore forming toxins, etc. Resealing or plasma membrane repair (PMR) is the emergency response required for cell survival. It is triggered by Ca2+ entering through the disruption, causing organelles such as lysosomes located underneath the plasma membrane to fuse rapidly with the adjacent plasma membrane. We have recently identified some of the molecular traffic machinery that is involved in this vital process. Specifically, we showed that 2 members of the Rab family of small GTPases, Rab3a and Rab10, are essential for lysosome exocytosis and PMR in cells challenged with a bacterial toxin, streptolysin-O (SLO)...
July 4, 2018: Small GTPases
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