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https://www.readbyqxmd.com/read/28822916/wip1-dependent-modulation-of-macrophage-migration-and-phagocytosis
#1
Yiting Tang, Bing Pan, Xin Zhou, Kai Xiong, Qian Gao, Lei Huang, Ying Xia, Ming Shen, Shulin Yang, Honglin Liu, Tao Tan, Jianjie Ma, Xuehong Xu, Yulian Mu, Kui Li
Macrophage accumulation within the vascular wall is a hallmark of atherosclerosis. Controlling macrophage conversion into foam cells remains a major challenge for treatment of atherosclerotic diseases. Here, we show that Wip1, a member of the PP2C family of Ser/Thr protein phosphatases, modulates macrophage migration and phagocytosis associated with atherosclerotic plaque formation. Wip1 deficiency increases migratory and phagocytic activities of the macrophage under stress conditions. Enhanced migration of Wip1(-/-) macrophages is mediated by Rac1-GTPase and PI3K/AKT signalling pathways...
August 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28822762/rab11a-is-required-for-porcine-reproductive-and-respiratory-syndrome-virus-induced-autophagy-to-promote-viral-replication
#2
Kai Wang, Shuaifeng Li, Tesfaye Worku, Xingjie Hao, Liaohan Yang, Shujun Zhang
Porcine reproductive and respiratory syndrome virus (PRRSV) is the leading virus known to cause massive economic loss in pig industry worldwide. In our previous study, transcriptional profiling of PRRSV-infected lung tissue of Tongcheng and landrane pigs, which have highly pathogenic PRRSV (HP-PRRSV) susceptibility differences, showed differential expression of Rab11a. The small GTPase Rab11a regulates intracellular membrane trafficking events involved in autophagy. However, the involvement of convergence of endosomal Rab11a and autophagy pathways during PRRSV infection is still unclear...
August 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28822221/brain-plasticity-cognitive-functions-and-neural-stem-cells-a-pivotal-role-for-the-brain-specific-neural-master-gene-srgap2-fam72
#3
Nguyen Thi Thanh Ho, Arne Kutzner, Klaus Heese
Due to an aging society with an increased dementia-induced threat to higher cognitive functions, it has become imperative to understand the molecular and cellular events controlling the memory and learning processes in the brain. Here, we suggest that the novel master gene pair |-SRGAP2-FAM72-| (SLIT-ROBO Rho GTPase activating protein 2 - family with sequence similarity to 72) reveals a new dogma for the regulation of neural stem cell (NSC) gene expression and is a distinctive player in the control of human brain plasticity...
August 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28821793/molecular-mechanisms-of-atlastin-mediated-er-membrane-fusion-revealed-by-a-fret-based-single-vesicle-fusion-assay
#4
Kyung Tae Kim, Yeojin Moon, Yunsu Jang, Kang Taek Lee, Changwook Lee, Youngsoo Jun, Sanghwa Lee
Homotypic fusion of endoplasmic reticulum membranes is driven by atlastin GTPases; however, the underlying mechanism remains largely unknown. Here, using a FRET-based single-vesicle fusion assay with liposomes bearing the yeast atlastin Sey1p, we investigated the molecular mechanisms of atlastin-mediated membrane tethering and fusion. Although Sey1p-bearing proteoliposomes frequently underwent membrane tethering in a GTP hydrolysis-dependent manner as reported in studies using bulk assays, only a small fraction of the tethered liposomes proceeded to fusion...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821742/rock-1-mediates-diabetes-induced-retinal-pigment-epithelial-and-endothelial-cell-blebbing-contribution-to-diabetic-retinopathy
#5
Pierre-Raphaël Rothschild, Sawsen Salah, Marianne Berdugo, Emmanuelle Gélizé, Kimberley Delaunay, Marie-Christine Naud, Christophe Klein, Alexandre Moulin, Michèle Savoldelli, Ciara Bergin, Jean-Claude Jeanny, Laurent Jonet, Yvan Arsenijevic, Francine Behar-Cohen, Patricia Crisanti
In diabetic retinopathy, the exact mechanisms leading to retinal capillary closure and to retinal barriers breakdown remain imperfectly understood. Rho-associated kinase (ROCK), an effector of the small GTPase Rho, involved in cytoskeleton dynamic regulation and cell polarity is activated by hyperglycemia. In one year-old Goto Kakizaki (GK) type 2 diabetic rats retina, ROCK-1 activation was assessed by its cellular distribution and by phosphorylation of its substrates, MYPT1 and MLC. In both GK rat and in human type 2 diabetic retinas, ROCK-1 is activated and associated with non-apoptotic membrane blebbing in retinal vessels and in retinal pigment epithelium (RPE) that respectively form the inner and the outer barriers...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821441/in-situ-detection-of-the-activation-of-rac1-and-rala-small-gtpases-in-mouse-adipocytes-by-immunofluorescent-microscopy-following-in-vivo-and-ex-vivo-insulin-stimulation
#6
Nobuyuki Takenaka, Yuma Nihata, Sho Ueda, Takaya Satoh
Rac1 has been implicated in insulin-dependent glucose uptake by mechanisms involving plasma membrane translocation of the glucose transporter GLUT4 in skeletal muscle. Although the uptake of glucose is also stimulated by insulin in adipose tissue, the role for Rac1 in adipocyte insulin signaling remains controversial. As a step to reveal the role for Rac1 in adipocytes, we aimed to establish immunofluorescent microscopy to detect the intracellular distribution of activated Rac1. The epitope-tagged Rac1-binding domain of a Rac1-specific target was utilized as a probe that specifically recognizes the activated form of Rac1...
August 15, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28819285/phosphorylation-of-sos1-on-tyrosine-1196-promotes-its-rac-gef-activity-and-contributes-to-bcr-abl-leukemogenesis
#7
S Gerboth, E Frittoli, A Palamidessi, F C Baltanas, S Mogjiborahman, J Rappsilber, C Giuliani, F Troglio, Y Rolland, G Pruneri, S Kreutmair, I Pallavicini, M Zobel, M Cinquanta, S Minucci, C Gomez, E Santos, A L Illert, G Scita
Son of Sevenless 1 (SOS1) is a dual guanine nucleotide exchange factor (GEF) that activates the small GTPases RAC and RAS. While the molecular mechanisms of RAS GEF catalysis have been unveiled, how SOS1 acquires RAC GEF activity and what is the physio-pathological relevance of this activity is much less understood. Here, we show that SOS1 is tyrosine phosphorylated on Y1196 by ABL. Phosphorylation of Y1196 controls SOS1 inter-molecular interaction, is required to promote the exchange of nucleotides on RAC in vitro, and for PDGF activation of RAC and RAC-dependent actin remodeling and cell migration...
August 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28819224/the-role-of-rho-gtpases-and-actin-polymerization-during-macrophage-tunneling-nanotube-biogenesis
#8
Samer J Hanna, Kessler McCoy-Simandle, Veronika Miskolci, Peng Guo, Michael Cammer, Louis Hodgson, Dianne Cox
Macrophage interactions with other cells, either locally or at distances, are imperative in both normal and pathological conditions. While soluble means of communication can transmit signals between different cells, it does not account for all long distance macrophage interactions. Recently described tunneling nanotubes (TNTs) are membranous channels that connect cells together and allow for transfer of signals, vesicles, and organelles. However, very little is known about the mechanism by which these structures are formed...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818525/whole-transcriptome-microarray-analysis-reveals-regulation-of-rab4-by-rbm5-in-neurons
#9
Travis C Jackson, Shawn E Kotermanski, Patrick M Kochanek
RNA binding motif 5 (RBM5) is a nuclear protein that modulates gene transcription and mRNA splicing in cancer cells. The brain is among the highest RBM5 expressing organ in the body but its mRNA target(s) or functions in the CNS have not been elucidated. Here we knocked down (KO) RBM5 in primary rat cortical neurons and analyzed total RNA extracts by gene microarray vs. neurons transduced with lentivirus to deliver control (non-targeting) shRNA. The mRNA levels of Sec23A (involved in ER-Golgi transport) and the small GTPase Rab4a (involved in endocytosis/protein trafficking) were increased in RBM5 KO neurons relative to controls...
August 14, 2017: Neuroscience
https://www.readbyqxmd.com/read/28815520/regulation-of-mitochondrial-dynamics-and-autophagy-by-the-mitochondria-associated-membrane
#10
Mitsuo Tagaya, Kohei Arasaki
Mitochondria are powerhouses and central to metabolism in cells. They are highly dynamic organelles that continuously fuse, divide, and move along the cytoskeleton to form the mitochondrial network. The fusion and fission are catalyzed by four dynamin-related GTPases in mammals that are controlled by a variety of protein-protein interactions and posttranslational modifications. Mitochondrial dynamics and metabolism are linked and regulate each other. Starvation induces mitochondrial elongation, which enables the mitochondria to produce energy more efficiently and to escape from autophagic degradation...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28814713/gelsolin-dysfunction-causes-photoreceptor-loss-in-induced-pluripotent-cell-and-animal-retinitis-pigmentosa-models
#11
Roly Megaw, Hashem Abu-Arafeh, Melissa Jungnickel, Carla Mellough, Christine Gurniak, Walter Witke, Wei Zhang, Hemant Khanna, Pleasantine Mill, Baljean Dhillon, Alan F Wright, Majlinda Lako, Charles Ffrench-Constant
Mutations in the Retinitis Pigmentosa GTPase Regulator (RPGR) cause X-linked RP (XLRP), an untreatable, inherited retinal dystrophy that leads to premature blindness. RPGR localises to the photoreceptor connecting cilium where its function remains unknown. Here we show, using murine and human induced pluripotent stem cell models, that RPGR interacts with and activates the actin-severing protein gelsolin, and that gelsolin regulates actin disassembly in the connecting cilium, thus facilitating rhodopsin transport to photoreceptor outer segments...
August 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28814662/irgm1-coordinately-regulates-autoimmunity-and-host-defense-at-select-mucosal-surfaces
#12
Kathleen M Azzam, Jennifer H Madenspacher, Derek W Cain, Lihua Lai, Kymberly M Gowdy, Prashant Rai, Kyathanahalli Janardhan, Natasha Clayton, Willie Cunningham, Heather Jensen, Preeyam S Patel, John F Kearney, Gregory A Taylor, Michael B Fessler
The pathogenesis of primary Sjogren's syndrome (SS), an autoimmune disease that targets the mucosa of exocrine tissues, is poorly understood. Although several mouse models have been developed that display features of SS, most of these are within the larger context of a lupus-like presentation. Immunity-related GTPase family M protein 1 (Irgm1) is an interferon-inducible cytoplasmic GTPase that is reported to regulate autophagy and mitochondrial homeostasis. Here, we report that naive Irgm1-/- mice display lymphocytic infiltration of multiple mucosal tissues including the lung in a manner reminiscent of SS, together with IgA class-predominant autoantibodies including anti-Ro and anti-La...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28814573/conserved-dynamics-of-chloroplast-cytoskeletal-ftsz-proteins-across-photosynthetic-lineages
#13
Allan D Terbush, Joshua S MacCready, Cheng Chen, Daniel C Ducat, Katherine W Osteryoung
The cytoskeletal FtsZ ring is critical for cell division in bacteria and chloroplast division in photosynthetic eukaryotes. While bacterial FtsZ rings are composed of a single FtsZ, except in the basal glaucophytes chloroplast division involves two heteropolymer-forming FtsZ isoforms--FtsZ1 and FtsZ2 in the green lineage and FtsZA and FtsZB in red algae. FtsZ1 and FtsZB probably arose by duplication of the more ancestral FtsZ2 and FtsZA, respectively. We expressed fluorescent fusions of FtsZ from diverse photosynthetic organisms in a heterologous system to compare their intrinsic assembly and dynamic properties...
August 16, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28811522/the-lichen-secondary-metabolite-atranorin-suppresses-lung-cancer-cell-motility-and-tumorigenesis
#14
Rui Zhou, Yi Yang, So-Yeon Park, Thanh Thi Nguyen, Young-Woo Seo, Kyung Hwa Lee, Jae Hyuk Lee, Kyung Keun Kim, Jae-Seoun Hur, Hangun Kim
Lichens are symbiotic organisms that produce various secondary metabolites. Here, different lichen extracts were examined to identify secondary metabolites with anti-migratory activity against human lung cancer cells. Everniastrum vexans had the most potent inhibitory activity, and atranorin was identified as an active subcomponent of this extract. Atranorin suppressed β-catenin-mediated TOPFLASH activity by inhibiting the nuclear import of β-catenin and downregulating β-catenin/LEF and c-jun/AP-1 downstream target genes such as CD44, cyclin-D1 and c-myc...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28810875/role-of-iqgap3-in-metastasis-and-epithelial-mesenchymal-transition-in-human-hepatocellular-carcinoma
#15
Yongjie Shi, Nan Qin, Qiang Zhou, Yanqiu Chen, Sicong Huang, Bo Chen, Gang Shen, Hongyun Jia
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide owing to its high rates of metastasis and recurrence. The oncogene IQ motif-containing GTPase activating protein 3 (IQGAP3) is ubiquitously overexpressed in several human cancers, including liver, ovary, lung, large intestine, gastric, bone marrow, and breast malignancies and is involved in the invasion and metastasis of cancer cells. Therefore, we aimed to determine the biological role and molecular mechanism of IQGAP3 in HCC...
August 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28808351/inhibition-of-the-mevalonate-pathway-augments-the-activity-of-pitavastatin-against-ovarian-cancer-cells
#16
Marwan Ibrahim Abdullah, Mohammed Najim Abed, Alan Richardson
Only 40% of patients with advanced ovarian cancer survive more than 5 years. We have previously shown that pitavastatin induces regression of ovarian cancer xenografts in mice. To evaluate whether the response of ovarian cancer cells to pitavastatin is potentiated by farnesyl diphosphate synthase inhibitors or geranylgeraniol transferase I inhibitors, we evaluated combinations of pitavastatin with zoledronic acid, risedronate and GGTI-2133 in a panel of ovarian cancer cells. Pitavastatin (IC50 = 0.6-14 μM), zoledronic acid (IC50 = 21-57 μM), risedronate (IC50 > 100 μM) or GGTI-2133 (IC50 > 25 μM) inhibited the growth of ovarian cancer cell cultures...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808135/mutations-in-eif5b-confer-thermosensitive-and-pleiotropic-phenotypes-via-translation-defects-in-arabidopsis-thaliana
#17
Liyuan Zhang, Xinye Liu, Kishor Gaikwad, Xiaoxia Kou, Fei Wang, Xuejun Tian, Mingming Xin, Zhongfu Ni, Qixin Sun, Huiru Peng, Elizabeth Vierling
The conserved eukaryotic translation initiation factor 5B, eIF5B, is a GTPase that acts late in translation initiation. We found that an Arabidopsis thaliana mutant sensitive to hot temperatures 3 (hot3-1), which behaves as wild type in the absence of stress but is unable to acclimate to high temperature, carries a missense mutation in eIF5B1 gene (At1g76810),, producing a temperature sensitive protein. A more severe, T-DNA insertion allele (hot3-2) causes pleiotropic developmental phenotypes. Surprisingly, Arabidopsis has three other eIF5B genes that do not substitute for eIF5B1; two of these appear to be in the process of pseudogenization...
August 14, 2017: Plant Cell
https://www.readbyqxmd.com/read/28808134/vps9a-activates-the-rab5-gtpase-ara7-to-confer-distinct-pre-and-post-invasive-plant-innate-immunity
#18
Mads Eggert Nielsen, Gerd Jürgens, Hans Thordal-Christensen
Plant innate immunity can effectively prevent the proliferation of filamentous pathogens. Papilla formation at the site of attack is essential for pre-invasive immunity; in post-invasive immunity the encasement of pathogen structures inside host cells can hamper disease. Whereas papillae are highly dependent on transcytosis of premade material, little is known about encasement formation. Here we show that endosome-associated VPS9a, the conserved guanine-nucleotide exchange factor activating Rab5 GTPases, is required for both pre- and post-invasive immunity against a non-adapted powdery mildew fungus (Blumeria graminis f...
August 14, 2017: Plant Cell
https://www.readbyqxmd.com/read/28808062/ablating-tbc1d1-impairs-contraction-induced-sarcolemmal-glucose-transporter-type-4-redistribution-but-not-insulin-mediated-responses-in-rats
#19
Jamie Whitfield, Sabina Paglialunga, Brennan K Smith, Paula M Miotto, Genevieve Simnett, Holly L Robson, Swati S Jain, Eric A F Herbst, Eric M Desjardins, David J Dyck, Lawrence L Spriet, Gregory R Steinberg, Graham P Holloway
TBC1 domain family member 1 (TBC1D1), a Rab GTPase-activating protein and paralogue of Akt substrate of 160 kDa (AS160), has been implicated in both insulin- and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (AICAR)-mediated glucose transporter type (GLUT4) translocation. However, the role of TBC1D1 in contracting muscle remains ambiguous. We therefore explored the metabolic consequence of ablating TBC1D1 in both resting and contracting skeletal muscles, utilizing a rat TBC1D1-KO model...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28808055/dynamin-dependent-amino-acid-endocytosis-activates-mechanistic-target-of-rapamycin-complex-1-mtorc1
#20
Shusaku Shibutani, Hana Okazaki, Hiroyuki Iwata
The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of protein synthesis and potential target for modifying cellular metabolism in various conditions, including cancer and aging. mTORC1 activity is tightly regulated by the availability of extracellular amino acids, and previous studies have revealed that amino acids in the extracellular fluid are transported to the lysosomal lumen. There, amino acids induce recruitment of cytoplasmic mTORC1 to the lysosome by the Rag GTPases, followed by mTORC1 activation by the small GTPase Ras homolog enriched in brain (Rheb)...
August 14, 2017: Journal of Biological Chemistry
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