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Small GTPases

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https://www.readbyqxmd.com/read/28448737/involvement-of-arhgef10-gef-for-rhoa-in-rab6-rab8-mediating-membrane-traffic
#1
Satoshi Shibata, Yui Teshima, Kenta Niimi, Shinobu Inagaki
Small GTPases play crucial roles in the maintenance of a homeostatic environment and appropriate movements of the cell. In these processes, the direct or indirect interaction between distinct small GTPases could be required for regulating mutual signaling pathways. In our recent study, ARHGEF10, known as a guanine nucleotide exchange factor (GEF) for RhoA, was indicated to interact with Rab6A and Rab8A, which are known to function in the exocytotic pathway, and colocalized with these Rabs at exocytotic vesicles...
April 27, 2017: Small GTPases
https://www.readbyqxmd.com/read/28430047/arf-gaps-and-molecular-motors
#2
Ruibai Luo, Christine E Reed, Jeffrey A Sload, Linda Wordeman, Paul A Randazzo, Pei-Wen Chen
Arf GTPase-activating proteins (Arf GAPs) were first identified as regulators of the small GTP-binding proteins ADP-ribosylation factors (Arfs). The Arf GAPs are a large family of proteins in metazoans, outnumbering the Arfs that they regulate. The members of the Arf GAP family have complex domain structures and some have been implicated in particular cellular functions, such as cell migration, or with particular pathologies, such as tumor invasion and metastasis. The specific effects of Arfs sometimes depend on the Arf GAP involved in their regulation...
April 21, 2017: Small GTPases
https://www.readbyqxmd.com/read/28410007/key-roles-of-arf-small-g-proteins-and-biosynthetic-trafficking-for-animal-development
#3
Francisco F Rodrigues, Tony J C Harris
Although biosynthetic trafficking can function constitutively, it also functions specifically for certain developmental processes. These processes require either a large increase to biosynthesis or the biosynthesis and targeted trafficking of specific players. We review the conserved molecular mechanisms that direct biosynthetic trafficking, and discuss how their genetic disruption affects animal development. Specifically, we consider Arf small G proteins, such as Arf1 and Sar1, and their coat effectors, COPI and COPII, and how these proteins promote biosynthetic trafficking for cleavage of the Drosophila embryo, the growth of neuronal dendrites and synapses, extracellular matrix secretion for bone development, lumen development in epithelial tubes, notochord and neural tube development, and ciliogenesis...
April 14, 2017: Small GTPases
https://www.readbyqxmd.com/read/28394692/exploring-the-iceberg-prospects-of-coordinated-myosin-v-and-actin-assembly-functions-in-transport-processes
#4
Tobias Welz, Eugen Kerkhoff
Spir actin nucleators and myosin V motor proteins were recently discovered to coexist in a protein complex. The direct interaction allows the coordinated activation of actin motor proteins and actin filament track generation at vesicle membranes. By now the cooperation of myosin V (MyoV) motors and Spir actin nucleation function has only been shown in the exocytic transport of Rab11 vesicles in metaphase mouse oocytes. Next to Rab11, myosin V motors however interact with a variety of Rab GTPases including Rab3, Rab8 and Rab10...
April 10, 2017: Small GTPases
https://www.readbyqxmd.com/read/28362242/arf-gaps-a-family-of-proteins-with-disparate-functions-that-converge-on-a-common-structure-the-integrin-adhesion-complex
#5
Teresa Vitali, Sofia Girald-Berlingeri, Paul A Randazzo, Pei-Wen Chen
ADP-ribosylation factors (Arfs) are members of the Ras GTPase superfamily. The function of Arfs is dependent on GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. Arf GAPs have been shown to be present in integrin adhesion complexes, which include focal adhesions. Integrin adhesion complexes are composed of integrins, scaffolding proteins and signaling proteins and regulate cell proliferation, survival, differentiation and migration...
March 31, 2017: Small GTPases
https://www.readbyqxmd.com/read/28350208/polarity-establishment-by-cdc42-key-roles-for-positive-feedback-and-differential-mobility
#6
Benjamin Woods, Daniel J Lew
Cell polarity is fundamental to the function of most cells. The evolutionarily conserved molecular machinery that controls cell polarity is centered on a family of GTPases related to Cdc42. Cdc42 becomes activated and concentrated at polarity sites, but studies in yeast model systems led to controversy on the mechanisms of polarization. Here we review recent studies that have clarified how Cdc42 becomes polarized in yeast. On one hand, findings that appeared to support a key role for the actin cytoskeleton and vesicle traffic in polarity establishment now appear to reflect the action of stress response pathways induced by cytoskeletal perturbations...
March 28, 2017: Small GTPases
https://www.readbyqxmd.com/read/28328290/cross-talk-between-rho-gtpases-and-pi3k-in-the-neutrophil
#7
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 while also being a key part of the inflammatory response. Chemokines induce neutrophil recruitment to inflammatory sites, where neutrophils perform several 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
#8
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
#9
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
#10
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
#11
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/28426288/post-translational-modifications-of-rab-gtpases
#12
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...
February 28, 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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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