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Small GTPases

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https://www.readbyqxmd.com/read/28328290/cross-talk-between-rho-gtpases-and-pi3k-in-the-neutrophil
#1
Barry McCormick, Julia Y Chu, Sonja Vermeren
Neutrophils are short-lived, abundant peripheral blood leukocytes that provide a first line of defense against bacterial and fungal infections whilst also being a key part of the inflammatory response. Chemokines induce neutrophil recruitment to inflammatory sites, where neutrophils perform a number of diverse functions that are aimed at fighting infections. Neutrophil effector functions are tightly regulated processes that are governed by an array of intracellular signaling pathways and initiated by receptor-ligand binding events...
March 22, 2017: Small GTPases
https://www.readbyqxmd.com/read/28304230/modular-regulation-of-rho-family-gtpases-in-development
#2
Marlis Denk-Lobnig, Adam C Martin
Rho family GTPase signaling regulates the actin cytoskeleton and is critical for behaviors that range from the cell to tissue-scale. A theme in Rho GTPase biology is that there are many more regulators, such as guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), than GTPases themselves. Here, we review different, modular cases where GEFs and GAPs function together to elicit precise spatial and temporal control of signaling. We focus on examples from metazoan development, where precise regulation of Rho GTPases is critical for proper tissue form and function...
March 17, 2017: Small GTPases
https://www.readbyqxmd.com/read/28301299/differential-role-for-pak1-and-pak4-during-the-invadopodia-lifecycle
#3
Nicole S Nicholas, Aikaterini Pipili, Michaela S Lesjak, Claire M Wells
PAK1 and PAK4 are members of the p-21 activated kinase family of serine/threonine kinases. PAK1 has previously been implicated in both the formation and disassembly of invasive cell protrusions, termed invadopodia. We recently reported a novel role for PAK4 during invadopodia maturation and confirmed a specific role for PAK1 in invadopodia formation; findings we will review here. Moreover, we found that PAK4 induction of maturation is delivered via interaction with the RhoA regulator PDZRho-GEF. We can now reveal that loss of PAK4 expression leads to changes in invadopodia dynamics...
March 16, 2017: Small GTPases
https://www.readbyqxmd.com/read/28287334/regulation-of-rho-gtpase-activity-at-the-leading-edge-of-migrating-cells-by-p190rhogap
#4
Aurélien Bidaud-Meynard, Fabien Binamé, Valérie Lagrée, Violaine Moreau
Cell migration, a key feature of embryonic development, immunity, angiogenesis, and tumor metastasis, is based on the coordinated regulation of actin dynamics and integrin-mediated adhesion. Rho GTPases play a major role in this phenomenon by regulating the onset and maintenance of actin-based protruding structures at cell leading edges (i.e. lamellipodia and filopodia) and contractile structures (i.e., stress fibers) at their trailing edge. While spatio-temporal analysis demonstrated the tight regulation of Rho GTPases at the migration front during cell locomotion, little is known about how the main regulators of Rho GTPase activity, such as GAPs, GEFs and GDIs, play a role in this process...
March 13, 2017: Small GTPases
https://www.readbyqxmd.com/read/28281933/spatial-regulation-of-araf-controls-the-mst2-hippo-pathway
#5
Jens Rauch, Walter Kolch
The RAF-MAPK signaling pathway regulates several very diverse cellular processes such as proliferation, differentiation, apoptosis, and transformation. While the canonical function of RAF kinases within the MAPK pathway is the activation of MEK, our group could demonstrate an important crosstalk between RAF signaling and the pro-apoptotic mammalian sterile 20-like kinase (MST2) tumor suppressor pathway in several cancer entities, including head and neck, colon, and breast. Here, the RAF kinases CRAF and ARAF sequester and inhibit the pro-apoptotic kinase MST2 independently of their own kinase activity...
March 10, 2017: Small GTPases
https://www.readbyqxmd.com/read/28287327/mechanism-of-cell-intrinsic-adaptation-to-adams-oliver-syndrome-gene-dock6-disruption-highlights-ubiquitin-like-modifier-isg15-as-a-regulator-of-rho-gtpases
#6
Berati Cerikan, Elmar Schiebel
DOCK6 is a RAC1/CDC42 guanine nucleotide exchange factor, however, little is known about its function and sub-cellular localization. DOCK6 regulates the balance between RAC1 and RHOA activity during cell adhesion and is important for CDC42-dependent mitotic chromosome alignment. Surprisingly, a cell intrinsic adaptation mechanism compensates for errors in these DOCK6 functions that arise as a consequence of prolonged DOCK6 depletion or complete removal in DOCK6 knockout cells. Down-regulation of the ubiquitin-like modifier ISG15 accounts for this adaptation...
February 23, 2017: Small GTPases
https://www.readbyqxmd.com/read/28146371/critical-importance-of-rab-proteins-for-synaptic-function
#7
Maria Lidia Mignogna, Patrizia D'Adamo
Neurons are highly polarized cells that exhibit one of the more complex morphology and function. Neuronal intracellular trafficking plays a key role in dictating the directionality and specificity of vesicle formation, transport and fusion, allowing the transmission of information in sophisticate cellular network. Thus, the integrity of protein trafficking and spatial organization is especially important in neuronal cells. RAB proteins, small monomeric GTPases belonging to the RAS superfamily, spatially and temporally orchestrate specific vesicular trafficking steps...
February 1, 2017: Small GTPases
https://www.readbyqxmd.com/read/28136018/co-existence-of-ras-activation-in-a-chemotactic-signal-transduction-pathway-and-in-an-autonomous-wave-forming-system
#8
Mary Ecke, Günther Gerisch
The activation of Ras is common to two activities in cells of Dictyostelium discoideum: the directed movement in a gradient of chemoattractant and the autonomous generation of propagating waves of actin polymerization on the substrate-attached cell surface. We produced large cells by electric-pulse induced fusion to simultaneously study both activities in one cell. For imaging, a fluorescent label for activated Ras was combined with labels for filamentous actin, PIP3, or PTEN. Chemotactic responses were elicited in a diffusion gradient of cyclic AMP...
January 31, 2017: Small GTPases
https://www.readbyqxmd.com/read/28135905/new-insights-into-the-function-of-rab-gtpases-in-the-context-of-exosomal-secretion
#9
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...
January 31, 2017: Small GTPases
https://www.readbyqxmd.com/read/28129089/activation-of-compensatory-pathways-via-rac2-in-the-absence-of-the-cdc42-effector-wiskott-aldrich-syndrome-protein-in-dendritic-cells
#10
Marisa A P Baptista, Lisa S Westerberg
There is extensive crosstalk between different Rho GTPases, including Cdc42, Rac1, and Rac2, and they can activate or inhibit the activity of each other. Dendritic cells express both Rac1 and Rac2. Due to posttranslational modification of lipid anchors, Rac1 localizes mainly to the plasma membrane whereas Rac2 localizes to the phagosomal membrane where it assembles the NADPH complex. Our recent study of primary immunodeficiency disease caused by mutations in the Cdc42 effector Wiskott-Aldrich syndrome protein (WASp) has shed light on the compensatory mechanisms between Rho GTPases and their effector proteins...
January 27, 2017: Small GTPases
https://www.readbyqxmd.com/read/28129039/coordination-of-synaptic-vesicle-trafficking-and-turnover-by-the-rab35-signaling-network
#11
Patricia Sheehan, Clarissa L Waites
Rab35 and the Rab35 network of GAPs, GEFs, and effectors are important regulators of membrane trafficking for a variety of cellular processes, from cytokinesis and phagocytosis to neurite outgrowth. In the past five years, components of this signaling network have also been implicated as critical mediators of synaptic vesicle (SV) recycling and protein homeostasis. Recent studies by several groups, including our own, have demonstrated that Rab35-mediated endosomal sorting is required for the degradation of SV proteins via the ESCRT pathway, thereby eliminating old or damaged proteins from the SV pool...
January 27, 2017: Small GTPases
https://www.readbyqxmd.com/read/28129038/regulation-of-small-gtpase-activity-by-g1-cyclins
#12
Neus Pedraza, Tània Cemeli, Ma Ventura Monserrat, Eloi Garí, Francisco Ferrezuelo
Together with a cyclin-dependent kinase (CDK) partner G1 cyclins control cell cycle entry by phosphorylating a number of nuclear targets and releasing a transcriptional program at the end of G1 phase. Yeast G1 cyclins also operate on cytoplasmic targets involved in the polarization of the cytoskeleton and vesicle trafficking. These processes are mainly controlled by the small GTPase Cdc42, and G1 cyclins regulate the activity of this and other small GTPases through the modulation of their regulators and effectors...
January 27, 2017: Small GTPases
https://www.readbyqxmd.com/read/28129037/multivalency-in-rab-effector-interactions
#13
Amrita Rai, Roger S Goody, Matthias P Müller
Rab proteins regulate vesicular transport in eukaryotic cells and establish connections to various cellular structures and processes by interacting with so-called effector molecules. Several of these effectors are known to not only bind a single Rab protein, but to be able to bind multiple different Rabs simultaneously. In this review we will give a short overview of effectors in general and (putative) functions of the aforementioned multivalent Rab:effector interactions.
January 27, 2017: Small GTPases
https://www.readbyqxmd.com/read/28129035/where-no-ras-has-gone-before-vps35-steers-n-ras-through-the-cytosol
#14
Mo Zhou, Mark R Philips
Ras is the best-studied member of the superfamily of small GTPases because of its role in cancer. Ras proteins transmit signals for proliferation, differentiation and survival. Three RAS genes encode 4 isoforms. All Ras isoforms have long been considered membrane bound, a localization required for function. Our recent study revealed that N-Ras differs from all other isoforms in being largely cytosolic even following modification with a prenyl lipid. Endogenous, cytosolic N-Ras chromatographed in both high and low molecular weight pools, a pattern that required prenylation, suggesting prenyl-dependent interaction with other proteins...
January 27, 2017: Small GTPases
https://www.readbyqxmd.com/read/28125340/rabs-set-the-stage-for-polarity
#15
Sara S Parker, Christopher Cox, Jean M Wilson
Cell polarity refers to the asymmetric localization of cellular components that allows cells to carry out their specialized functions, be they epithelial barrier function, transmission of action potentials in nerve cells, or modulation of the immune response. The establishment and maintenance of cell polarity requires the directed trafficking of membrane proteins and lipids - essential processes that are mediated by Rab GTPases. Interestingly, several of the Rabs that impact polarity are present in the earliest eukaryotes, and the Rab polarity repertoire has expanded as cells have become more complex...
January 26, 2017: Small GTPases
https://www.readbyqxmd.com/read/28125336/new-insights-into-mechanisms-of-nuclear-translocation-of-g-protein-coupled-receptors
#16
Vikrant K Bhosle, José Carlos Rivera, Sylvain Chemtob
The G-protein coupled receptor (GPCR) signaling was long believed to involve activation of receptor exclusively at the cell surface, followed by its binding to heterotrimeric G-proteins and arrestins to trigger various intracellular signaling cascades, and termination of signaling by internalization of the receptor. It is now accepted that many GPCRs continue to signal after internalization in the endosomes. Since the breakthrough discoveries of nuclear binding sites for their ligands in 1980s, several GPCRs have been detected at cell nuclei...
January 26, 2017: Small GTPases
https://www.readbyqxmd.com/read/28125332/the-versatility-of-rhoa-activities-in-neural-differentiation
#17
Arie Horowitz, Junning Yang, Jingli Cai, Lorraine Iacovitti
In this commentary we discuss a paper we published recently on the activities of the GTPase RhoA during neural differentiation of murine embryonic stem cells, and relate our findings to previous studies. We narrate how we found that RhoA impedes neural differentiation by inhibiting the production as well as the secretion of noggin, a soluble factor that antagonizes bone morphogenetic protein. We discuss how the questions we tried to address shaped the study, and how embryonic stem cells isolated from a genetically modified mouse model devoid of Syx, a RhoA-specific guanine exchange factor, were used to address them...
January 26, 2017: Small GTPases
https://www.readbyqxmd.com/read/28125329/role-of-rab-gtpases-in-the-export-trafficking-of-g-protein-coupled-receptors
#18
Guansong Wang, Zhe Wei, Guangyu Wu
G protein-coupled receptors (GPCRs) constitute a superfamily of cell surface receptors that regulate a variety of cell functions. As the cell surface is the functional destination for most GPCRs, the cell surface targeting process represents a crucial checkpoint in controlling the functionality of the receptors. However, the molecular mechanisms underlying the cell surface delivery of newly synthesized GPCRs remain poorly understood. In this review, we will highlight the role of Rab GTPases in GPCR cell surface transport, particularly post-Golgi traffic, and discuss the underlying molecular mechanisms...
January 26, 2017: Small GTPases
https://www.readbyqxmd.com/read/28118081/rabs-on-the-fly-functions-of-rab-gtpases-during-development
#19
Sara Caviglia, David Flores-Benitez, Johanna Lattner, Stefan Luschnig, Marko Brankatschk
The organisation of intracellular transport processes is adapted specifically to different cell types, developmental stages, and physiological requirements. Some protein traffic routes are universal to all cells and constitutively active, while other routes are cell-type specific, transient, and induced under particular conditions only. Small GTPases of the Rab (Ras related in brain) subfamily are conserved across eukaryotes and regulate most intracellular transit pathways. The complete sets of Rab proteins have been identified in model organisms, and molecular principles underlying Rab functions have been uncovered...
January 24, 2017: Small GTPases
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
#20
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
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