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https://www.readbyqxmd.com/read/28918952/a-dual-function-for-prickle-in-regulating-frizzled-stability-during-feedback-dependent-amplification-of-planar-polarity
#1
Samantha J Warrington, Helen Strutt, Katherine H Fisher, David Strutt
The core planar polarity pathway coordinates epithelial cell polarity during animal development, and loss of its activity gives rise to a range of defects, from aberrant morphogenetic cell movements to failure to correctly orient structures, such as hairs and cilia. The core pathway functions via a mechanism involving segregation of its protein components to opposite cells ends, where they form asymmetric intracellular complexes that couple cell-cell polarity. This segregation is a self-organizing process driven by feedback interactions between the core proteins themselves...
September 7, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28899395/role-of-rab5-in-the-formation-of-macrophage-derived-foam-cell
#2
Lokwern Chan, Jin Hong, Junjie Pan, Jian Li, Zhichao Wen, Haiming Shi, Jianping Ding, Xinping Luo
BACKGROUND: Foam cells play a key role in the occurrence and pathogenesis of atherosclerosis. Its formation starts with the ingestion of oxidized low-density lipoprotein (oxLDL). The process is associated with Ras related protein in brain 5 (Rab5) which plays a critical role in regulating endocytosis and early endosomal trafficking. Base on this, we presumed that Rab5 might participate in the maturation of foam cell. The aim of this study is to investigate the effect of Rab5 on macrophage cholesterol during the evolvement of macrophage when induced by oxLDL to the formation of foam cell...
September 12, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28878211/assay-to-visualize-specific-protein-oxidation-reveals-spatio-temporal-regulation-of-shp2
#3
Ryouhei Tsutsumi, Jana Harizanova, Rabea Stockert, Katrin Schröder, Philippe I H Bastiaens, Benjamin G Neel
Reactive oxygen species are produced transiently in response to cell stimuli, and function as second messengers that oxidize target proteins. Protein-tyrosine phosphatases are important reactive oxygen species targets, whose oxidation results in rapid, reversible, catalytic inactivation. Despite increasing evidence for the importance of protein-tyrosine phosphatase oxidation in signal transduction, the cell biological details of reactive oxygen species-catalyzed protein-tyrosine phosphatase inactivation have remained largely unclear, due to our inability to visualize protein-tyrosine phosphatase oxidation in cells...
September 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28874679/the-endosomal-neuronal-proteins-nsg1-neep21-and-nsg2-p19-are-itinerant-not-resident-proteins-of-dendritic-endosomes
#4
Chan Choo Yap, Laura Digilio, Lloyd McMahon, Bettina Winckler
Membrane traffic critically regulates most aspects of neuronal function. Neurons express many neuronal-specific proteins that regulate membrane traffic, including the poorly understood small transmembrane proteins neural-specific gene 1 and 2 (Nsg1/NEEP21 and Nsg2/P19). Nsg1 has been implicated in regulating endosomal recycling and sorting of several important neuronal receptors. Nsg2 is largely unstudied. At steady-state, Nsg1 and Nsg2 only partially co-localize with known endosomal compartments, and it was suggested that they mark a neuronal-specific endosome...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28872124/in-vitro-polymerization-of-f-actin-on-early-endosomes
#5
Olivia Muriel, Cameron Christopher Scott, Jorge Larios, Vicent Mercier, Jean Gruenberg
Many early endosome functions, particularly cargo protein sorting and membrane deformation, depend on patches of short F-actin filaments nucleated onto the endosomal membrane. We have established a microscopy-based in vitro assay that reconstitutes the nucleation and polymerization of F-actin on early endosomal membranes in test tubes, thus rendering this complex series of reactions amenable to genetic and biochemical manipulations. Endosomal fractions are prepared by floatation in sucrose gradients from cells expressing the early endosomal protein GFP-RAB5...
August 28, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28865956/developmentally-regulated-gtp-binding-protein-2-is-required-for-stabilization-of-rac1-positive-membrane-tubules
#6
Muralidharan Mani, Unn Hwa Lee, Nal Ae Yoon, Eun Hye Yoon, Byung Ju Lee, Wha Ja Cho, Jeong Woo Park
Previously we have reported that developmentally regulated GTP-binding protein 2 (DRG2) localizes on Rab5 endosomes and plays an important role in transferrin (Tfn) recycling. We here identified DRG2 as a key regulator of membrane tubule stability. At 30 min after Tfn treatment, DRG2 localized to membrane tubules which were enriched with phosphatidylinositol 4-monophosphate [PI(4)P] and did not contain Rab5. DRG2 interacted with Rac1 more strongly with GTP-bound Rac1 and tubular localization of DRG2 depended on Rac1 activity...
September 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28860274/wdr91-is-a-rab7-effector-required-for-neuronal-development
#7
Kai Liu, Ruxiao Xing, Youli Jian, Zhiyang Gao, Xinli Ma, Xiaojuan Sun, Yang Li, Meng Xu, Xin Wang, Yudong Jing, Weixiang Guo, Chonglin Yang
Early-to-late endosome conversion, which is essential for delivery of endosomal cargoes to lysosomes, requires switching of early endosome-specific Rab5 and PtdIns3P to late endosome-specific Rab7 and PtdIns(3,5)P2 In this study, we identify the WD40-repeat protein WDR91 as a Rab7 effector that couples Rab switching with PtdIns3P down-regulation on endosomes. Loss of WDR91 greatly increases endosomal PtdIns3P levels, arresting endosomes at an intermediate stage and blocking endosomal-lysosomal trafficking. WDR91 is recruited to endosomes by interacting with active guanosine triphosophate-Rab7 and inhibits Rab7-associated phosphatidylinositol 3-kinase activity...
August 31, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28844737/structural-templating-of-j-aggregates-visualizing-bis-monoacylglycero-phosphate-domains-in-live-cells
#8
Gary C H Mo, Christopher M Yip
Identifying the key structural and dynamical determinants that drive the association of biomolecules, whether in solution, or perhaps more importantly in a membrane environment, has critical implications for our understanding of cellular dynamics, processes, and signaling. With recent advances in high-resolution imaging techniques, from the development of new molecular labels to technical advances in imaging methodologies and platforms, researchers are now reaping the benefits of being able to directly characterize and quantify local dynamics, structures, and conformations in live cells and tissues...
August 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28808134/vps9a-activates-the-rab5-gtpase-ara7-to-confer-distinct-pre-and-post-invasive-plant-innate-immunity
#9
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/28751526/the-salivary-peptide-histatin-1-promotes-endothelial-cell-adhesion-migration-and-angiogenesis
#10
Pedro Torres, Jorge Díaz, Maximiliano Arce, Patricio Silva, Pablo Mendoza, Pablo Lois, Alfredo Molina-Berríos, Gareth I Owen, Verónica Palma, Vicente A Torres
Saliva is a key factor that contributes to the high efficiency of wound healing in the oral mucosa. This is not only attributed to physical cues but also to the presence of specific peptides in the saliva, such as histatins. Histatin-1 is a 38 aa antimicrobial peptide, highly enriched in human saliva, which has been previously reported to promote the migration of oral keratinocytes and fibroblasts in vitro However, the participation of histatin-1 in other crucial events required for wound healing, such as angiogenesis, is unknown...
July 27, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28732201/small-molecules-for-early-endosome-specific-patch-clamping
#11
Cheng-Chang Chen, Elisabeth S Butz, Yu-Kai Chao, Yulia Grishchuk, Lars Becker, Stefan Heller, Susan A Slaugenhaupt, Martin Biel, Christian Wahl-Schott, Christian Grimm
To resolve the subcellular distribution of endolysosomal ion channels, we have established a novel experimental approach to selectively patch clamp Rab5 positive early endosomes (EE) versus Rab7/LAMP1-positive late endosomes/lysosomes (LE/LY). To functionally characterize ion channels in endolysosomal membranes with the patch-clamp technique, it is important to develop techniques to selectively enlarge the respective organelles. We found here that two small molecules, wortmannin and latrunculin B, enlarge Rab5-positive EE when combined but not Rab7-, LAMP1-, or Rab11 (RE)-positive vesicles...
July 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28724764/rab5-and-rab11-are-required-for-clathrin-dependent-endocytosis-of-japanese-encephalitis-virus-in-bhk-21-cells
#12
Chun-Chun Liu, Yun-Na Zhang, Zhao-Yao Li, Jin-Xiu Hou, Jing Zhou, Lin Kan, Bin Zhou, Pu-Yan Chen
During infection Japanese Encephalitis Virus generally enters host cells via receptor-mediated clathrin dependent endocytosis. The trafficking of JEV within endosomes is controlled by Rab GTPases, but which Rab proteins are involved in JEV entry into BHK-21 cells is unknown. In this study, entry and post-internalization of JEV were analyzed using biochemical inhibitors, RNA interference and dominant negative mutants. Our data demonstrate that JEV entry into BHK-21 cells depends on clathrin, dynamin, and cholesterol, but not caveolae or macropinocytosis...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28722510/bnip3l-dependent-mitophagy-accounts-for-mitochondrial-clearance-during-3-factors-induced-somatic-cell-reprogramming
#13
Ge Xiang, Liang Yang, Qi Long, Keshi Chen, Haite Tang, Yi Wu, Zihuang Liu, Yanshuang Zhou, Juntao Qi, Lingjun Zheng, Wenbo Liu, Zhongfu Ying, Weimin Fan, Hongyan Shi, Hongmei Li, Xiaobing Lin, Mi Gao, Jinglei Liu, Feixiang Bao, Linpeng Li, Lifan Duan, Min Li, Xingguo Liu
Induced pluripotent stem cells (iPSCs) have fewer and immature mitochondria than somatic cells and mainly rely on glycolysis for energy source. During somatic cell reprogramming, somatic mitochondria and other organelles get remodeled. However, events of organelle remodeling and interaction during somatic cell reprogramming have not been extensively explored. We show that both SKP/SKO (Sox2, Klf4, Pou5f1/Oct4) and SKPM/SKOM (SKP/SKO plus Myc/c-Myc) reprogramming lead to decreased mitochondrial mass but with different kinetics and by divergent pathways...
July 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28696827/isolation-of-rab5-positive-endosomes-reveals-a-new-mitochondrial-degradation-pathway-utilized-by-bnip3-and-parkin
#14
Babette C Hammerling, Sarah E Shires, Leonardo J Leon, Melissa Q Cortez, Åsa B Gustafsson
Degradation of mitochondria is an important cellular quality control mechanism mediated by two distinct pathways: one involving Parkin-mediated ubiquitination and the other dependent on mitophagy receptors. It is known that mitochondria are degraded by the autophagy pathway; however, we recently reported that the small GTPase Rab5 and early endosomes also participate in Parkin-mediated mitochondrial clearance. Here, we have developed a protocol to isolate Rab5-positive vesicles from cells for proteomics analysis and provide additional data confirming that mitophagy regulators and mitochondrial proteins are present in these vesicles...
July 11, 2017: Small GTPases
https://www.readbyqxmd.com/read/28696297/mtorc1-activates-srebp-2-by-suppressing-cholesterol-trafficking-to-lysosomes-in-mammalian-cells
#15
Walaa Eid, Kristin Dauner, Kevin C Courtney, AnneMarie Gagnon, Robin J Parks, Alexander Sorisky, Xiaohui Zha
mTORC1 is known to activate sterol regulatory element-binding proteins (SREBPs) including SREBP-2, a master regulator of cholesterol synthesis. Through incompletely understood mechanisms, activated mTORC1 triggers translocation of SREBP-2, an endoplasmic reticulum (ER) resident protein, to the Golgi where SREBP-2 is cleaved to translocate to the nucleus and activate gene expression for cholesterol synthesis. Low ER cholesterol is a well-established trigger for SREBP-2 activation. We thus investigated whether mTORC1 activates SREBP-2 by reducing cholesterol delivery to the ER...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28686604/boosting-efferocytosis-in-alveolar-space-using-bcg-vaccine-to-protect-host-against-influenza-pneumonia
#16
Sanjay Mukherjee, Renuka Subramaniam, Han Chen, Anthony Smith, Shiva Keshava, Homayoun Shams
Efferocytosis by alveolar phagocytes (APs) is pivotal in maintenance of lung homeostasis. Increased efferocytosis by APs results in protection against lethal acute lung injury due to pulmonary infections whereas defective efferocytosis by APs results in chronic lung inflammation. In this report, we show that pulmonary delivery of Bacillus Calmette-Guerin (BCG) significantly enhances efferocytosis by APs. Increased efferocytosis by APs maintains lung homeostasis and protects mice against lethal influenza pneumonia...
2017: PloS One
https://www.readbyqxmd.com/read/28650718/subversion-of-rab5-regulated-autophagy-by-the-intracellular-pathogen-ehrlichia-chaffeensis
#17
Yasuko Rikihisa
Intracellular pathogens often exploit RAB functions to establish a safe haven in which to survive and proliferate. Ehrlichia chaffeensis, an obligatory intracellular bacterium, resides in specialized membrane-bound inclusions that have early endosome-like characteristics, e.g., resident RAB5 GTPase and RAB5 effectors, including VPS34 (the catalytic subunit of class III phosphatidylinositol 3-kinase), but the inclusions lack late endosomal or lysosomal markers. Within inclusions, Ehrlichia obtains host-derived nutrients by inducing RAB5-regulated autophagy using Ehrlichia translocated factor-1 deployed by its type IV secretion system...
June 26, 2017: Small GTPases
https://www.readbyqxmd.com/read/28642463/acute-loss-of-the-hepatic-endo-lysosomal-system-in-vivo-causes-compensatory-changes-in-iron-homeostasis
#18
Christoph Metzendorf, Anja Zeigerer, Sarah Seifert, Richard Sparla, Bahar Najafi, François Canonne-Hergaux, Marino Zerial, Martina U Muckenthaler
Liver cells communicate with the extracellular environment to take up nutrients via endocytosis. Iron uptake is essential for metabolic activities and cell homeostasis. Here, we investigated the role of the endocytic system for maintaining iron homeostasis. We specifically depleted the small GTPase Rab5 in the mouse liver, causing a transient loss of the entire endo-lysosomal system. Strikingly, endosome depletion led to a fast reduction of hepatic iron levels, which was preceded by an increased abundance of the iron exporter ferroportin...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28638803/peptide-nucleic-acid-knockdown-and-intra-host-cell-complementation-of-ehrlichia-type-iv-secretion-system-effector
#19
Pratibha Sharma, Omid Teymournejad, Yasuko Rikihisa
Survival of Ehrlichia chaffeensis depends on obligatory intracellular infection. One of the barriers to E. chaffeensis research progress has been the inability, using conventional techniques, to generate knock-out mutants for genes essential for intracellular infection. This study examined the use of Peptide Nucleic Acids (PNAs) technology to interrupt type IV secretion system (T4SS) effector protein expression in E. chaffeensis followed by intracellular complementation of the effector to determine its requirement for infection...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28634871/rabies-virus-co-localizes-with-early-rab5-and-late-rab7-endosomal-proteins-in-neuronal-and-sh-sy5y-cells
#20
Waqas Ahmad, Yingying Li, Yidi Guo, Xinyu Wang, Ming Duan, Zhenhong Guan, Zengshan Liu, Maolin Zhang
Rabies virus (RABV) is a highly neurotropic virus that follows clathrin-mediated endocytosis and pH-dependent pathway for trafficking and invasion into endothelial cells. Early (Rab5, EEA1) and late (Rab7, LAMP1) endosomal proteins play critical roles in endosomal sorting, maturity and targeting various molecular cargoes, but their precise functions in the early stage of RABV neuronal infection remain elusive. In this study, the relationship between enigmatic entry of RABV with these endosomal proteins into neuronal and SH-SY5Y cells was investigated...
June 2017: Virologica Sinica
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