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Small GTPases

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https://www.readbyqxmd.com/read/28103137/cap-gly-proteins-contribute-to-microtubule-dependent-trafficking-via-interactions-with-the-c-terminal-aromatic-residue-of-%C3%AE-tubulin
#1
Annie Andrieux, Laurence Aubry, Cécile Boscheron
In mammals, the C-terminal tyrosine residue of α-tubulin is subjected to removal/re-addition cycles resulting in tyrosinated microtubules and detyrosinated Glu-microtubules. CLIP170 and its yeast ortholog (Bik1) interact weakly with Glu-microtubules. Recently, we described a Microtubule- Rho1- and Bik1-dependent mechanism involved in Snc1 routing. Here, we further show a contribution of the yeast p150Glued ortholog (Nip100) in Snc1 trafficking. Both CLIP170 and p150Glued are CAP-Gly-containing proteins that belong to the microtubule +end-tracking protein family (known as +Tips)...
January 19, 2017: Small GTPases
https://www.readbyqxmd.com/read/28060560/harnessing-membrane-trafficking-to-promote-cancer-spreading-and-invasion-the-case-of-rab2a
#2
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 tumours of epithelial origin to acquire a mesenchymal program of invasiveness. However, the critical molecular hubs utilized 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...
January 6, 2017: Small GTPases
https://www.readbyqxmd.com/read/28055293/epidermal-activation-of-the-small-gtpase-rac1-in-psoriasis-pathogenesis
#3
Mårten C G Winge, M Peter Marinkovich
The small GTPase Ras-related C3 botulinum toxin substrate 1 (RAC1) plays a central role in skin homeostasis, including barrier function, wound healing and inflammatory responses. Psoriasis is a common skin disease characterized by deregulation of these functions, and affected skin exhibit keratinocyte hyperproliferation, inflammation and immune cell infiltration. Although psoriasis is often triggered by environmental stimulus, there is a strong genetic association with genes expressed in both immune cells and keratinocytes, of which several are linked to Rac1 signaling...
January 5, 2017: Small GTPases
https://www.readbyqxmd.com/read/28055292/molecular-control-of-rab-activity-by-gefs-gaps-and-gdi
#4
Matthias P Müller, Roger S Goody
Rab proteins are the major regulators of vesicular trafficking in eukaryotic cells. Their activity can be tightly controlled within cells: Regulated by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), they switch between an active GTP-bound state and an inactive GDP-bound state, interacting with downstream effector proteins only in the active state. Additionally, they can bind to membranes via C-terminal prenylated cysteine residues and they can be solubilized and shuttled between membranes by chaperone-like molecules called GDP dissociation inhibitors (GDIs)...
January 5, 2017: Small GTPases
https://www.readbyqxmd.com/read/28005455/small-gtpases-controlling-autophagy-related-membrane-traffic-in-yeast-and-metazoans
#5
Szabolcs Takáts, Attila Boda, Tamás Csizmadia, Gábor Juhász
During macroautophagy, the phagophore-mediated formation of autophagosomes and their subsequent fusion with lysosomes requires extensive transformation of the endomembrane system. Membrane dynamics in eukaryotic cells is regulated by small GTPase proteins including Arfs and Rabs. The small GTPase proteins that regulate autophagic membrane traffic are mostly conserved in yeast and metazoans, but there are also several differences. In this mini-review, we compare the small GTPase network of yeast and metazoan cells that regulates autophagy, and point out the similarities and differences in these organisms...
December 22, 2016: Small GTPases
https://www.readbyqxmd.com/read/28001501/the-small-gtpase-arf6-regulates-protein-trafficking-to-control-cellular-function-during-development-and-in-disease
#6
Allie H Grossmann, Helong Zhao, Noah Jenkins, Weiquan Zhu, Jackson R Richards, Jae Hyuk Yoo, Jacob M Winter, Bianca Rich, Tara M Mleynek, Dean Y Li, Shannon J Odelberg
The activation of the small GTPase ARF6 has been implicated in promoting several pathological processes related to vascular instability and tumor formation, growth, and metastasis. ARF6 also plays a vital role during embryonic development. Recent studies have suggested that ARF6 carries out these disparate functions primarily by controlling protein trafficking within the cell. ARF6 helps direct proteins to intracellular or extracellular locations where they function in normal cellular responses during development and in pathological processes later in life...
December 21, 2016: Small GTPases
https://www.readbyqxmd.com/read/27936345/targeting-integrin-linked-kinase-to-suppress-oncogenic-kras-signaling-in-pancreatic-cancer
#7
Po-Chen Chu, Samuel K Kulp, Tanios Bekaii-Saab, Ching-Shih Chen
Although oncogenic KRAS represents a therapeutically relevant target in pancreatic cancer, it is deemed "non-druggable" because of the intrinsic difficulty in designing direct inhibitors of KRAS. Our recent work demonstrated a KRAS-integrin-linked kinase (ILK) regulatory feedback loop that allows pancreatic cancer cells to regulate KRAS expression and to interact with the tumor microenvironment to promote aggressive phenotype. KRAS induces E2F1-mediated transcriptional activation of ILK expression, and ILK, in turn, controls KRAS expression via hnRNPA1, which binds and destabilizes the G-quadruplex in the KRAS promoter...
December 9, 2016: Small GTPases
https://www.readbyqxmd.com/read/27898263/genetic-alterations-affecting-gtpases-and-t-cell-receptor-signaling-in-peripheral-t-cell-lymphomas
#8
Rebecca L Boddicker, Gina L Razidlo, Andrew L Feldman
Peripheral T-cell lymphomas (PTCLs) are rare, heterogeneous tumors with poor response to standard therapy and few targeted treatments available. The identification of mutations in the T-cell receptor (TCR) signaling pathway that either directly or indirectly affect Ras- and Rho-family GTPases is an emerging theme across PTCL subtypes. This review summarizes the role of GTPases in TCR signaling and highlights the constellation of mutations in this pathway among PTCLs. In particular, focus is given to the functional impact of the mutations and opportunities for targeted therapy...
November 29, 2016: Small GTPases
https://www.readbyqxmd.com/read/27880081/an-emerging-role-for-iqgap1-in-tight-junction-control
#9
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...
November 23, 2016: Small GTPases
https://www.readbyqxmd.com/read/27880072/oncogenic-kras-and-the-egfr-loop-in-pancreatic-carcinogenesis-a-connection-to-licensing-nodes
#10
Christian Schneeweis, Matthias Wirth, Dieter Saur, Maximilian Reichert, Günter Schneider
EGFR signaling has a critical role in oncogenic KRAS-driven tumorigenesis of the pancreas, whereas it is dispensable in other organs. The complex signaling network engaged by oncogenic KRAS and its modulation by EGFR signaling, remains incompletely understood. In order to study early signaling events activated by oncogenic KRAS in the pancreas, we recently developed a novel model system based on murine primary pancreatic epithelial cells enabling the time-specific expression of mutant Kras(G12D) from its endogenous promoter...
November 23, 2016: Small GTPases
https://www.readbyqxmd.com/read/27875100/the-small-gtpase-ral-orchestrates-mvb-biogenesis-and-exosome-secretion
#11
Vincent Hyenne, Michel Labouesse, Jacky G Goetz
Extracellular vesicles are novel mediators of cell-cell communication. They are present in all species and involved in physiological and pathological processes. One class of extracellular vesicles, the exosomes, originate from an endosomal compartment, the MultiVesicular Body (MVB), and are released from the cell upon fusion of the MVB with the plasma membrane. Although different molecular mechanisms have been associated with MVB biogenesis and exosome secretion, how they coordinate remains poorly documented...
November 22, 2016: Small GTPases
https://www.readbyqxmd.com/read/27875099/the-rhob-small-gtpase-in-physiology-and-disease
#12
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...
November 22, 2016: Small GTPases
https://www.readbyqxmd.com/read/27854154/small-gtpases-in-c-elegans-metabolism
#13
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...
November 17, 2016: Small GTPases
https://www.readbyqxmd.com/read/27849131/spatial-rho-regulation-molecular-mechanisms-controlling-the-gap-protein-dlc3
#14
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/27768524/c9orf72-plays-a-central-role-in-rab-gtpase-dependent-regulation-of-autophagy
#15
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...
October 21, 2016: Small GTPases
https://www.readbyqxmd.com/read/27768516/rho-gtpases-in-mammalian-spinal-neural-tube-closure
#16
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...
October 21, 2016: Small GTPases
https://www.readbyqxmd.com/read/27763815/diverted-recycling-shigella-subversion-of-rabs
#17
Noelia Lopez 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...
October 20, 2016: Small GTPases
https://www.readbyqxmd.com/read/27763811/small-gtpase-proteins-in-macroautophagy
#18
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...
October 20, 2016: Small GTPases
https://www.readbyqxmd.com/read/27754752/rhoa-controls-retinoid-signaling-by-rock-dependent-regulation-of-retinol-metabolism
#19
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...
October 18, 2016: Small GTPases
https://www.readbyqxmd.com/read/27754746/the-distinct-traits-of-extracellular-vesicles-generated-by-transformed-cells
#20
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...
October 18, 2016: Small GTPases
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