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Small GTPases

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https://www.readbyqxmd.com/read/28632996/taking-control-hijacking-of-rab-gtpases-by-intracellular-bacterial-pathogens
#1
Stefania Spanò, Jorge E Galán
Intracellular bacterial pathogens survive and replicate within specialized eukaryotic cell organelles. To establish their intracellular niches these pathogens have adopted sophisticated strategies to control intracellular membrane trafficking. Since Rab-family GTPases are critical regulators of endocytic and secretory membrane trafficking events, many intracellular pathogens have evolved specific mechanisms to modulate or hijack Rab GTPases dynamics and trafficking functions. One such strategy is the delivery of bacterial effectors through specialized machines to specifically target Rab GTPases...
June 20, 2017: Small GTPases
https://www.readbyqxmd.com/read/28632994/role-of-the-small-gtpase-rap1-in-signal-transduction-cell-dynamics-and-bacterial-infection
#2
Hubert Hilbi, Arjan Kortholt
Rap1 belongs to the Ras family of small GTPases, which are involved in a multitude of cellular signal transduction pathways and have extensively been linked to cancer biogenesis and metastasis. The small GTPase is activated in response to various extracellular and intracellular cues. Rap1 has conserved functions in Dictyostelium discoideum amoeba and mammalian cells, which are important for cell polarity, substrate and cell-cell adhesion and other processes that involve the regulation of cytoskeletal dynamics...
June 20, 2017: Small GTPases
https://www.readbyqxmd.com/read/28632992/targeting-the-rhogtpase-rock-pathway-for-the-treatment-of-vhl-hif-pathway-driven-cancers
#3
Jordan M Thompson, Jaime Landman, Olga V Razorenova
The loss of the von Hippel-Lindau (VHL) tumor-suppressor is a major driver of Clear Cell Renal Cell Carcinoma (CC-RCC) resulting in the stabilization and overactivation of hypoxia inducible factors (HIFs). ROCK 1 is a well-known protein serine/threonine kinase which is recognized as having a role in cancer including alterations in cell motility, metastasis and angiogenesis. As a function of the later effect, we recently investigated and identified a synthetic lethal interaction between VHL loss and ROCK1 inhibition in CC-RCC that is dependent on HIF overactivation...
June 20, 2017: Small GTPases
https://www.readbyqxmd.com/read/28632484/rab-gtpases-and-their-interacting-protein-partners-structural-insights-into-rab-functional-diversity
#4
Olena Pylypenko, Hussein Hammich, I-Mei Yu, Anne Houdusse
Rab molecular switches are key players in defining membrane identity and regulating intracellular trafficking events in eukaryotic cells. In spite of their global structural similarity, Rab-family members acquired particular features that allow them to perform specific cellular functions. The overall fold and local sequence conservations enable them to utilize a common machinery for prenylation and recycling; while individual Rab structural differences determine interactions with specific partners such as GEFs, GAPs and effector proteins...
June 20, 2017: Small GTPases
https://www.readbyqxmd.com/read/28628388/coordination-of-ampa-receptor-trafficking-by-rab-small-gtpases
#5
Angelika Hausser, Katalin Schlett
Synaptic connections in the brain are continuously weakened or strengthened in response to changes in neuronal activity. This process, known as synaptic plasticity, is the cellular basis for learning and memory, and is thought to be altered in several neuronal disorders. An important aspect of synaptic plasticity is the tightly controlled trafficking and synaptic targeting of the AMPA-type glutamate receptors, which are the major mediators of fast excitatory transmission in the brain. This review addresses the role of Rab GTPases in AMPA receptor trafficking in neurons under basal conditions and during activity-induced synaptic plasticity, especially during long-term potentiation (LTP) and long-term depression (LTD)...
June 19, 2017: Small GTPases
https://www.readbyqxmd.com/read/28628382/unpaking-runx3-functions-both-sides-of-the-coin
#6
Arun Kumar, Sandhya Sundaram, Suresh K Rayala, Ganesh Venkatraman
Post translational modifications of RUNX3 have been shown to play an important role in directing RUNX3 functions. In this review we highlight the phosphorylation dependent functions of RUNX3 as regulated by PAK1 and its implications on tumorigenesis.
June 19, 2017: Small GTPases
https://www.readbyqxmd.com/read/28622072/new-model-for-the-interaction-of-iqgap1-with-cdc42-and-rac1
#7
Kazem Nouri, David J Timson, Mohammad R Ahmadian
The specific and rapid formation of protein complexes, involving IQGAP family proteins, is essential for diverse cellular processes, such as adhesion, polarization, and directional migration. Although CDC42 and RAC1, prominent members of the RHO GTPase family, have been implicated in binding to and activating IQGAP1, the exact nature of this protein-protein recognition process has remained obscure. Here, we propose a mechanistic framework model that is based on a multiple-step binding process, which is a prerequisite for the dynamic functions of IQGAP1 as a scaffolding protein and a critical mechanism in temporal regulation and integration of cellular pathways...
June 16, 2017: Small GTPases
https://www.readbyqxmd.com/read/28613117/heavy-subunit-of-cell-surface-gal-galnac-lectin-hgl-undergoes-degradation-via-endo-lysosomal-compartments-in-entamoeba-histolytica
#8
Kuldeep Verma, Sunando Datta
The human gut parasite Entamoeba histolytica uses a multifunctional virulence factor, Hgl, a cell surface transmembrane receptor subunit of Gal/GalNAc lectin that contributes to adhesion, invasion, cytotoxicity and immune response in the host. At present, the physiological importance of Hgl receptor is mostly known for pathogenicity of E. histolytica. However, the molecular mechanisms of Hgl trafficking events and their association with the intracellular membrane transport machinery are largely unknown. We employed biochemical and microscopy-based assays to understand the Hgl trafficking in the amoebic trophozoites...
June 14, 2017: Small GTPases
https://www.readbyqxmd.com/read/28613115/contribution-of-phosphatidylserine-to-rho1-and-pkc1-related-repolarization-of-the-actin-cytoskeleton-under-stressed-conditions-in-saccharomyces-cerevisiae
#9
Wataru Nomura, Yoshiharu Inoue
The budding yeast Saccharomyces cerevisiae undergoes polarized cell growth, which is established in association with actin polarization. Rho1, one of the Rho-type GTPases in S. cerevisiae, is crucial for maintaining polarized cell growth and actin polarization and controlling the downstream signaling pathway, the Pkc1-Mpk1 MAP kinase cascade, through a physical interaction with Pkc1, the sole protein kinase C in this yeast. The Pkc1-Mpk1 MAP kinase cascade is important for the repolarization of actin under heat shock-stressed conditions...
June 14, 2017: Small GTPases
https://www.readbyqxmd.com/read/28609201/opposite-functions-of-stat3-and-smad3-in-regulating-tiam1-expression-in-th17-cells
#10
Thomas Buttrick, Samia J Khoury, Wassim Elyaman
We recently showed that Tiam1 expression is induced in pro-inflammatory T helper 17 (Th17) cells differentiated with interleukin (IL)-6 and TGF-β1, and together with Rac1 promote Th17 cell development and autoimmunity in a mouse model of multiple sclerosis. Here we found that STAT3 and Smad3, downstream transcription factors of IL-6 and TGF-β1, respectively, play opposing roles in regulating Tiam1 transcription in CD4(+) T-cells. While IL-6-STAT3 signaling promotes Tiam1 expression, TGF-β1-Smad3 induces the opposite outcome...
June 13, 2017: Small GTPases
https://www.readbyqxmd.com/read/28586283/mkl1-dependent-gene-activation-is-sufficient-to-induce-actin-cap-assembly
#11
Ketan Thakar, Christopher W Carroll
Actin-dependent forces mechanically control both the position and shape of the nucleus. While the mechanisms that establish nuclear position are well defined, less understood is how actin filaments determine nuclear shape. We recently showed that nuclear envelope-spanning LINC complexes promote stress fiber assembly by activating the small GTPase RhoA and Mkl1-dependent gene activation. We now report that a subset of these stress fibers associate with the apical face of the nuclear envelope through LINC complexes that contain the inner nuclear membrane protein Sun2...
June 6, 2017: Small GTPases
https://www.readbyqxmd.com/read/28524815/anchoring-high-concentrations-of-syngap-at-postsynaptic-densities-via-liquid-liquid-phase-separation
#12
Menglong Zeng, Guanhua Bai, Mingjie Zhang
SynGAP, encoded by SYNGAP1, is a Ras/Rap GTPase activator specifically expressed in the nervous systems. SynGAP is one of the most abundant proteins in the postsynaptic densities (PSDs) of excitatory synapses and acts as a critical synaptic activity brake by tuning down synaptic GTPase activities. Mutations of SYNGAP1 have been frequently linked to brain disorders including intellectual disability, autisms, and seizure. SynGAP has been shown to undergo fast dispersions from synapses in response to stimulations, a strategy that neurons use to control the specific activities of the enzyme within the tiny, semi-open compartments in dendritic spines...
May 19, 2017: Small GTPases
https://www.readbyqxmd.com/read/28524754/arf-gtpase-interplay-with-rho-gtpases-in-regulation-of-the-actin-cytoskeleton
#13
Vikash Singh, Anthony C Davidson, Peter J Hume, Daniel Humphreys, Vassilis Koronakis
The Arf and Rho subfamilies of small GTPases are nucleotide-dependent molecular switches that act as master regulators of vesicular trafficking and the actin cytoskeleton organization. Small GTPases control cell processes with high fidelity by acting through distinct repertoires of binding partners called effectors. While we understand a great deal about how these GTPases act individually, relatively little is known about how they cooperate, especially in the control of effectors. This review highlights how Arf GTPases collaborate with Rac1 to regulate actin cytoskeleton dynamics at the membrane via recruiting and activating the Wave Regulatory Complex (WRC), a Rho effector that underpins lamellipodia formation and macropinocytosis...
May 19, 2017: Small GTPases
https://www.readbyqxmd.com/read/28521592/molecular-perturbation-strategies-to-examine-spatiotemporal-features-of-rho-gef-and-rho-gtpase-activity-in-living-cells
#14
Joachim Goedhart, Jakobus van Unen
Much of our current knowledge of Rho GTPase networks and the regulation by Rho guanine exchange factors (Rho GEFs) and Rho GTPase activating proteins (Rho GAPs) is based on population-based techniques. Over the last decades, technologies that enable single cell analysis with high spatial and temporal resolution have revealed that Rho GTPase activity in cells is regulated on second timescales and at submicrometer length scales. Therefore, perturbation methods with matching spatial and temporal resolution are crucial to further our understanding of Rho GTPase signaling...
May 19, 2017: Small GTPases
https://www.readbyqxmd.com/read/28498728/a-family-affair-a-ral-exocyst-centered-network-links-ras-rac-rho-signaling-to-control-cell-migration
#15
Giulia Zago, Marco Biondini, Jacques Camonis, Maria Carla Parrini
Cell migration is central to many developmental, physiologic and pathological processes, including cancer progression. The Ral GTPases (RalA and RalB) which act down-stream the Ras oncogenes, are key players in the coordination between membrane trafficking and actin polymerization. A major direct effector of Ral, the exocyst complex, works in polarized exocytosis and is at the center of multiple protein-protein interactions that support cell migration by promoting protrusion formation, front-rear polarization, and extra-cellular matrix degradation...
May 12, 2017: Small GTPases
https://www.readbyqxmd.com/read/28489965/evidence-for-the-subsynaptic-zone-as-a-preferential-site-for-chrn-recycling-at-neuromuscular-junctions
#16
Franziska Wild, Muzamil Majid Khan, Rüdiger Rudolf
Vertebrate skeletal muscle contraction is mediated by nicotinic acetylcholine receptors (CHRN). Endocytosis and recycling of CHRN regulate their proper abundance at nerve-muscle synapses, i.e. neuromuscular junctions. Recent work showed that RAB5 is essential for CHRN endocytosis. Here, using in vivo-imaging of endocytosed CHRN and RAB-GFP fusion proteins, we deliver evidence for differential effects of RAB5-GFP, RAB4-GFP, and RAB11-GFP on CHRN endocytosis. Furthermore, while newly endocytosed CHRN colocalized with RAB5-GFP over large stretches of muscle fibers, RAB4-GFP and RAB11-GFP colocalized with endocytosed CHRN almost exclusively at neuromuscular junctions...
May 10, 2017: Small GTPases
https://www.readbyqxmd.com/read/28489964/specific-activation-of-plekhg2-induced-serum-response-element-dependent-gene-transcription-by-four-and-a-half-lim-domains-fhl-1-but-not-fhl2-or-fhl3
#17
Masashi Nishikawa, Katsuya Sato, Shun Nakano, Hisashi Yamakawa, Takahiro Nagase, Hiroshi Ueda
PLEKHG2 is a Gβγ- and Gαs-dependent guanine nucleotide exchange factor for Rac1 and Cdc42 small GTPases and has been shown to mediate signaling pathways such as those for actin cytoskeletal reorganization and serum response element (SRE)-dependent gene transcription. We have shown that the four-and-a-half LIM domains (FHL) 1 acts as a positive regulator of PLEKHG2. Here, we evaluated the other FHL family members and found that the FHL1A specifically regulate the PLEKHG2 activity. Moreover, FHL1A further enhanced Gβγ- and PLEKHG2-induced SRE-dependent gene transcription, whereas FHL1A partially restored the attenuated PLEKHG2-induced SRE-dependent gene transcription by Gαs...
May 10, 2017: Small GTPases
https://www.readbyqxmd.com/read/28489961/the-role-of-exo70-in-exocytosis-and-beyond
#18
Yueyao Zhu, Bin Wu, Wei Guo
The exocyst complex mediates the tethering of secretory vesicles to the plasma membrane before SNARE-mediated membrane fusion. Recent studies have implicated the exocyst in a wide range of cellular processes. Particularly, research on the Exo70 subunit of the complex has linked the function of the exocyst in exocytosis to cell adhesion, migration and invasion. In this review, we will discuss the recent work on how Exo70 regulates these cellular processes, and how small GTPases and kinases interact with Exo70 to orchestrate its function in exocytosis and cytoskeleton organization...
May 10, 2017: Small GTPases
https://www.readbyqxmd.com/read/28489960/swap70-is-a-universal-gef-like-adapter-for-tethering-actin-to-phagosomes
#19
Maksim V Baranov, Natalia H Revelo, Daniëlle R J Verboogen, Martin Ter Beest, Geert van den Bogaart
We recently identified a key role for SWAP70 as the tethering factor stabilizing F-actin filaments on the surface of phagosomes in human dendritic cells by interacting both with Rho-family GTPases and the lipid phosphatidylinositol (3,4)-bisphosphate. In this study, we aimed to investigate whether this role of SWAP70 was general among immune phagocytes. Our data reveal that SWAP70 is recruited to early phagosomes of macrophages and dendritic cells from both human and mouse. The putative inhibitor of SWAP70 sanguinarine blocked phagocytosis and F-actin polymerization, supporting a key role for SWAP70 in phagocytosis as demonstrated previously with knock-down...
May 10, 2017: Small GTPases
https://www.readbyqxmd.com/read/28471300/rab-gtpases-and-cell-division
#20
Paulius Gibieža, Rytis Prekeris
Cytokinesis is a complex cellular process that leads to a physical separation of two daughter cells. The key to a successful cytokinesis is a coordinated reorganization of cellular cytoskeleton and membrane trafficking pathways. Consequently, Rab GTPases recently emerged as major regulators of cellular division. Rabs belong to a superfamily of small monomeric GTPases that regulate a diverse array of cellular functions. Rabs in particular are well-established regulators of membrane transport and have been shown to mediate several membrane transport steps including vesicle formation, molecular motor-dependent vesicle transport and targeting of transport vesicles and organelles to their correct destinations...
May 4, 2017: Small GTPases
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