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https://www.readbyqxmd.com/read/28228250/stratum-a-homolog-of-the-human-gef-mss4-partnered-with-rab8-controls-the-basal-restriction-of-basement-membrane-proteins-in-epithelial-cells
#1
Olivier Devergne, Gina H Sun, Trudi Schüpbach
The basement membrane (BM), a sheet of extracellular matrix lining the basal side of epithelia, is essential for epithelial cell function and integrity, yet the mechanisms that control the basal restriction of BM proteins are poorly understood. In epithelial cells, a specialized pathway is dedicated to restrict the deposition of BM proteins basally. Here, we report the identification of a factor in this pathway, a homolog of the mammalian guanine nucleotide exchange factor (GEF) Mss4, which we have named Stratum...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28214467/paxillin-a-crossroad-in-pathological-cell-migration
#2
REVIEW
Ana María López-Colomé, Irene Lee-Rivera, Regina Benavides-Hidalgo, Edith López
Paxilllin is a multifunctional and multidomain focal adhesion adapter protein which serves an important scaffolding role at focal adhesions by recruiting structural and signaling molecules involved in cell movement and migration, when phosphorylated on specific Tyr and Ser residues. Upon integrin engagement with extracellular matrix, paxillin is phosphorylated at Tyr31, Tyr118, Ser188, and Ser190, activating numerous signaling cascades which promote cell migration, indicating that the regulation of adhesion dynamics is under the control of a complex display of signaling mechanisms...
February 18, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28214347/involvement-of-the-guanine-nucleotide-exchange-factor-vav3-in-central-nervous-system-development-and-plasticity
#3
Annika Ulc, Christine Gottschling, Ina Schäfer, David Wegrzyn, Simon van Leeuwen, Veronika Luft, Jacqueline Reinhard, Andreas Faissner
Small GTP-hydrolysing enzymes (GTPases) of the RhoA family play manifold roles in cell biology and are regulated by upstream guanine nucleotide exchange factors (GEFs). Herein, we focus on the GEFs of the Vav subfamily. Vav1 was originally described as a protooncogene of the hematopoietic lineage. The GEFs Vav2 and Vav3 are more broadly expressed in various tissues. In particular, the GEF Vav3 may play important roles in the developing nervous system during the differentiation of neural stem cells into the major lineages, namely neurons, oligodendrocytes and astrocytes...
February 18, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28210903/role-of-exchange-protein-directly-activated-by-camp-epac1-in-breast-cancer-cell-migration-and-apoptosis
#4
Naveen Kumar, Sonal Gupta, Surbhi Dabral, Shailja Singh, Seema Sehrawat
Despite the current progress in cancer research and therapy, breast cancer remains the leading cause of mortality among half a million women worldwide. Migration and invasion of cancer cells are associated with prevalent tumor metastasis as well as high mortality. Extensive studies have powerfully established the role of prototypic second messenger cAMP and its two ubiquitously expressed intracellular cAMP receptors namely the classic protein kinaseA/cAMP-dependent protein kinase (PKA) and the more recently discovered exchange protein directly activated by cAMP/cAMP-regulated guanine nucleotide exchange factor (EPAC/cAMP-GEF) in cell migration, cell cycle regulation, and cell death...
February 16, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28202288/tiam1-vav2-rac1-axis-a-tug-of-war-between-islet-function-and-dysfunction
#5
REVIEW
Anjaneyulu Kowluru
Glucose-stimulated insulin secretion [GSIS] from the islet β-cell involves a well-orchestrated interplay between metabolic and cationic events. It is well established that intracellular generation of adenine and guanine nucleotide triphosphates [e.g., ATP and GTP] represents one of the requisite signaling steps in GSIS. The small molecular mass GTP-binding proteins [G-proteins; e.g., Rac1 and Cdc42] have been shown to regulate islet β-cell function including actin cytoskeletal remodeling and fusion of insulin granules with the plasma membrane for GSIS to occur...
February 12, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28196833/characterization-of-the-activation-of-small-gtpases-by-their-gefs-on-membranes-using-artificial-membrane-tethering
#6
François Peurois, Simon Veyron, Yann Ferrandez, Ilham Ladid, Sarah Benabdi, Mahel Zeghouf, Gérald Peyroche, Jacqueline Cherfils
Attachment of active, GTP-bound small GTPases to membranes by post-translational lipid modifications is pivotal for their ability to process and propagate information in cells. However, generating and manipulating lipidated GTPases has remained difficult, which has limited our quantitative understanding of their activation by GEFs and their termination by GAPs. Here we replaced the lipid modification by a histidine tag in eleven full-length, human small GTPases belonging to the Arf, Rho and Rab families, which allowed to tether them to nickel-lipid containing membranes and characterize the kinetics of their activation by GEFs...
February 14, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28196591/nuclear-pkc%C3%AE-ect2-rac1-and-ribosome-biogenesis-a-novel-axis-in-lung-tumorigenesis
#7
Martin J Baker, Mariana Cooke, Marcelo G Kazanietz
The RhoGEF Ect2 controls cell division and exerts oncogenic functions in multiple cancers. In this issue of Cancer Cell, Justilien et al. report that Ect2 is required for lung tumorigenesis and identified a role for this GEF in ribosomal RNA (rRNA) synthesis that is mediated by Rac1 and PKCι-dependent phosphorylation.
February 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28195531/multiplex-image-based-autophagy-rnai-screening-identifies-smcr8-as-ulk1-kinase-activity-and-gene-expression-regulator
#8
Jennifer Jung, Arnab Nayak, Véronique Schaeffer, Tatjana Starzetz, Achim K Kirsch, Stefan Müller, Ivan Dikic, Michel Mittelbronn, Christian Behrends
Autophagy is an intracellular recycling and degradation pathway that depends on membrane trafficking. Rab GTPases are central for autophagy but their regulation especially through the activity of Rab GEFs remains largely elusive. We employed a RNAi screen simultaneously monitoring different populations of autophagosomes and identified 34 out of 186 Rab GTPase, GAP and GEF family members as potential autophagy regulators, amongst them SMCR8. SMCR8 uses overlapping binding regions to associate with C9ORF72 or with a C9ORF72-ULK1 kinase complex holo-assembly, which function in maturation and formation of autophagosomes, respectively...
February 14, 2017: ELife
https://www.readbyqxmd.com/read/28193206/inducing-goat-pluripotent-stem-cells-with-four-transcription-factor-mrnas-that-activate-endogenous-promoters
#9
Hao Chen, Qisheng Zuo, Yingjie Wang, Jiuzhou Song, Huilin Yang, Yani Zhang, Bichun Li
BACKGROUND: Traditional approaches for generating goat pluripotent stem cells (iPSCs) suffer from complexity and low preparation efficiency. Therefore, we tried to derive goat iPSCs with a new method by transfecting exogenous Oct4, Sox2, Klf4 and c-Myc mRNAs into goat embryonic fibroblasts (GEFs), and explore the mechanisms regarding the transcription regulation of the reprogramming factors in goat iPSCs induction. RESULTS: mRNAs of the four reprogramming factors were transfected into GEFs, and were localized in nucleus with approximately 90% transfection efficiency...
February 13, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/28192756/scn1a-clinical-spectrum-includes-the-self-limited-focal-epilepsies-of-childhood
#10
Sara Kivity, Karen L Oliver, Zaid Afawi, John A Damiano, Todor Arsov, Melanie Bahlo, Samuel F Berkovic
INTRODUCTION: Amongst autosomal dominant genetic epilepsy with febrile seizures plus (GEFS+) families, SCN1A variants are the most common genetic cause. Initially regarded as a generalized form of epilepsy, the GEFS+ spectrum is now known to include some focal epilepsies, but it is generally not conceptualized as extending to the self-limited focal epilepsies of childhood, such as Panayiotopoulos syndrome. There are, however, three reports of SCN1A variants in Panayiotopoulos syndrome...
February 4, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28188273/the-rho-gtpase-ropgef2-rop7-rop2-pathway-activated-by-phyb-suppresses-red-light-induced-stomatal-opening
#11
Wei Wang, Zhao Liu, Li-Juan Bao, Sha-Sha Zhang, Chun-Guang Zhang, Xin Li, Hai-Xia Li, Xiao-Lu Zhang, Atle Magnar Bones, Zhenbiao Yang, Yu-Ling Chen
Circadian rhythm of stomatal aperture is mainly regulated by light/darkness. Blue and red light induce stomatal opening through different mechanisms that are mediated by special receptors. ROP2, a member of Rho GTPase family in Arabidopsis (Arabidopsis Thaliana), has been found to negatively regulate light-induced stomatal opening. However, the upstream guanine nucleotide exchange factor (GEF) RopGEFs have not been revealed, and it is unclear which photoreceptor is required for the action of RopGEFs-ROPs. Here, we showed that RopGEF2 acted as a negative regulator in phytochrome B (phyB)-mediated red light-induced stomatal opening...
February 10, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28186670/rab7-may-be-a-novel-therapeutic-target-for-neurologic-diseases-as-a-key-regulator-in-autophagy
#12
REVIEW
Haixia Wen, Lixuan Zhan, Siyuan Chen, Long Long, En Xu
Macroautophagy is an evolutionally conserved membrane trafficking pathway that delivers intracellular materials to lysosomes for degradation and recycling. Rab7, as a member of the Rab GTPase superfamily, has a unique role in the regulation of macroautophagy, especially in modulating autophagy flux. The functional states of Rab7 generally switch between GTP-bound and GDP-bound states under the control of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Activated GTP-Rab7 is capable of regulating autophagosome formation, autophagosome transportation along microtubules, endosome and autophagosome maturation, as well as lysosome biogenesis via interacting with its effector molecules...
February 10, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28185854/a-dual-role-for-the-rhogef-ephexin5-in-regulation-of-dendritic-spine-outgrowth
#13
A M Hamilton, J T Lambert, L K Parajuli, O Vivas, D K Park, I S Stein, J N Jahncke, M E Greenberg, S S Margolis, K Zito
The outgrowth of new dendritic spines is closely linked to the formation of new synapses, and is thought to be a vital component of the experience-dependent circuit plasticity that supports learning. Here, we examined the role of the RhoGEF Ephexin5 in driving activity-dependent spine outgrowth. We found that reducing Ephexin5 levels increased spine outgrowth, and increasing Ephexin5 levels decreased spine outgrowth in a GEF-dependent manner, suggesting that Ephexin5 acts as an inhibitor of spine outgrowth...
February 6, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28179147/structural-basis-of-pdz-mediated-chemokine-receptor-cxcr2-scaffolding-by-guanine-nucleotide-exchange-factor-pdz-rhogef
#14
Nicholas Spellmon, Joshua Holcomb, Andrea Niu, Vishakha Choudhary, Xiaonan Sun, Yingxue Zhang, Junmei Wan, Maysaa Doughan, Stephanie Hayden, Fatme Hachem, Joseph Brunzelle, Chunying Li, Zhe Yang
The CXC chemokine receptor 2 (CXCR2) is a G protein coupled receptor mediating interleukin-8 chemotactic signaling and plays an important role in neutrophil mobility and tumor migration. However, efficient CXCR2 signaling requires PDZ domain-mediated scaffolding of signaling complexes at the plasma membrane and functional coupling of the signaling to specific downstream signaling pathways, in which only one PDZ protein has been characterized to interact with CXCR2. Here, we identified five novel CXCR2-binding PDZ-containing proteins, among which PDZ-RhoGEF is of particular interest because this PDZ and RGS-containing guanine nucleotide exchange factor (GEF) is also involved in cell signaling and mobility...
February 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28154176/a-kras-gtpase-k104q-mutant-retains-downstream-signaling-by-offsetting-defects-in-regulation
#15
Guowei Yin, Samantha Kistler, Samuel D George, Nora Kuhlmann, Leslie Garvey, Minh Huynh, Rachel K Bagni, Michael Lammers, Channing J Der, Sharon L Campbell
The KRAS GTPase plays a critical role in control of cellular growth. The activity of KRAS is regulated by guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs), and also by posttranslational modification. Lysine 104 in KRAS can be modified by ubiquitylation and acetylation, but the role this residue in intrinsic KRAS function has not been well characterized. We find that lysine 104 is important for GEF recognition, as mutations at this position impair GEF-mediated nucleotide exchange...
January 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28132723/eb1-contributes-to-proper-front-to-back-polarity-in-neutrophil-like-hl-60-cells
#16
Matthias Samereier, Michael Schleicher, Heike Roth, Doris Brechtefeld, Barbara Walzog, Annette Müller-Taubenberger
Directed migration of leukocytes towards a chemotactic source is largely dependent on coordinated actin cytoskeleton functions that provide the driving forces at the cell front and enable contractility at the rear. In contrast to the force-generating properties of the actin cytoskeleton, the microtubule network assumes a regulatory function in balancing front-to-back polarity. In migrating neutrophils, microtubules are mostly concentrated at the cell rear, and previously published work suggested that microtubules are stabilized and kept in place by a mechanism involving Cdc42, WASP, CD11b, and the end-binding protein 1 (EB1)...
January 19, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28130497/mechanisms-of-impaired-neutrophil-migration-by-micrornas-in-myelodysplastic-syndromes
#17
Meiwan Cao, Yayoi Shikama, Hideo Kimura, Hideyoshi Noji, Kazuhiko Ikeda, Tomoyuki Ono, Kazuei Ogawa, Yasuchika Takeishi, Junko Kimura
In myelodysplastic syndromes (MDS), functional defects of neutrophils result in high mortality because of infections; however, the molecular basis remains unclear. We recently found that miR-34a and miR-155 were significantly increased in MDS neutrophils. To clarify the effects of the aberrant microRNA expression on neutrophil functions, we introduced miR-34a, miR-155, or control microRNA into neutrophil-like differentiated HL60 cells. Ectopically introduced miR-34a and miR-155 significantly attenuated migration toward chemoattractants fMLF and IL-8, but enhanced degranulation...
January 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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/28115158/mdia2-and-cxcl12-cxcr4-chemokine-signaling-intersect-to-drive-tumor-cell-amoeboid-morphological-transitions
#19
Meghan M Wyse, Silvia Goicoechea, Rafael Garcia-Mata, Andrea L Nestor-Kalinoski, Kathryn M Eisenmann
Morphological plasticity in response to environmental cues in migrating cancer cells requires F-actin cytoskeletal rearrangements. Conserved formin family proteins play critical roles in cell shape, tumor cell motility, invasion and metastasis, in part, through assembly of non-branched actin filaments. Diaphanous-related formin-2 (mDia2/Diaph3/Drf3/Dia) regulates mesenchymal-to-amoeboid morphological conversions and non-apoptotic blebbing in tumor cells by interacting with its inhibitor diaphanous-interacting protein (DIP), and disrupting cortical F-actin assembly and bundling...
January 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28114311/rhogtpase-regulators-orchestrate-distinct-stages-of-synaptic-development
#20
Samuel Martin-Vilchez, Leanna Whitmore, Hannelore Asmussen, Jessica Zareno, Rick Horwitz, Karen Newell-Litwa
Small RhoGTPases regulate changes in post-synaptic spine morphology and density that support learning and memory. They are also major targets of synaptic disorders, including Autism. Here we sought to determine whether upstream RhoGTPase regulators, including GEFs, GAPs, and GDIs, sculpt specific stages of synaptic development. The majority of examined molecules uniquely regulate either early spine precursor formation or later maturation. Specifically, an activator of actin polymerization, the Rac1 GEF β-PIX, drives spine precursor formation, whereas both FRABIN, a Cdc42 GEF, and OLIGOPHRENIN-1, a RhoA GAP, regulate spine precursor elongation...
2017: PloS One
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