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Syntaxin 17

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https://www.readbyqxmd.com/read/28933649/legionella-blocks-autophagy-by-cleaving-stx17-syntaxin-17
#1
Kohei Arasaki, Mitsuo Tagaya
Pathogens subvert host defense systems including autophagy and apoptosis for their survival and proliferation. Legionella pneumophila is a Gram-negative bacterium that grows in alveolar macrophages and causes severe pneumonia. Early during infection Legionella secretes effector proteins that convert the plasma membrane-derived vacuole containing Legionella into an endoplasmic reticulum (ER)-like replicative vacuole. These vacuoles ultimately fuse with the ER, where the pathogen replicates. Recently, we showed that one of the effectors, Lpg1137, is a serine protease that targets the mitochondria-associated ER membrane (MAM) and degrades STX17 (syntaxin 17), a SNARE implicated in macroautophagy/autophagy as well as mitochondria dynamics and membrane trafficking in fed cells...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28677644/2bc-non-structural-protein-of-enterovirus-a71-interacts-with-snare-proteins-to-trigger-autolysosome-formation
#2
Jeffrey K F Lai, I-Ching Sam, Pauline Verlhac, Joël Baguet, Eeva-Liisa Eskelinen, Mathias Faure, Yoke Fun Chan
Viruses have evolved unique strategies to evade or subvert autophagy machinery. Enterovirus A71 (EV-A71) induces autophagy during infection in vitro and in vivo. In this study, we report that EV-A71 triggers autolysosome formation during infection in human rhabdomyosarcoma (RD) cells to facilitate its replication. Blocking autophagosome-lysosome fusion with chloroquine inhibited virus RNA replication, resulting in lower viral titres, viral RNA copies and viral proteins. Overexpression of the non-structural protein 2BC of EV-A71 induced autolysosome formation...
July 4, 2017: Viruses
https://www.readbyqxmd.com/read/28625264/-suppressive-effect-of-corm-2-on-platelet-%C3%AE-granule-exocytosis-in-sepsis-via-snare-munc18b-complex-formation
#3
Mingfeng Zhuang, Bingwei Sun, Dadong Liu, Yuan Shi
OBJECTIVE: To investigate the suppressive effect of carbon monoxide-releasing molecule II (CORM-2) on LPS induced platelet α-granule exocytosis in sepsis via soluble N-ethylmaleimide-sensitive factor attached protein receptor/mammalian uncoordinated 18b (SNARE/Munc18b) complex formation. METHODS: Blood was collected from healthy volunteers' cubital vein, then platelets were isolated by differential centrifugation. Platelets were randomly divided into 5 groups. The control group did not undergo any treatment, the LPS group received 10 mg/L LPS simulation, the CORM-2 group and iCORM-2 group underwent LPS simulation and immediate administration of CORM-2 (10 μmol/L and 50 μmol/L) or iCORM-2 (50 μmol/L), respectively...
February 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28598244/accumulation-of-undegraded-autophagosomes-by-expression-of-dominant-negative-stx17-syntaxin-17-mutants
#4
Masaaki Uematsu, Taki Nishimura, Yuriko Sakamaki, Hayashi Yamamoto, Noboru Mizushima
Macroautophagy/autophagy, which is one of the main degradation systems in the cell, is mediated by a specialized organelle, the autophagosome. Purification of autophagosomes before fusion with lysosomes is important for both mechanistic and physiological studies of the autophagosome. Here, we report a simple method to accumulate undigested autophagosomes. Overexpression of the autophagosomal Qa-SNARE STX17 (syntaxin 17) lacking the N-terminal domain (NTD) or N-terminally tagged GFP-STX17 causes accumulation of autophagosomes...
August 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28579390/fluorescent-markers-of-various-organelles-in-the-wheat-pathogen-zymoseptoria-tritici
#5
S Kilaru, M Schuster, W Ma, G Steinberg
Development of novel strategies to control fungal plant pathogens requires understanding of their cellular organisation and biology. Live cell imaging of fluorescent organelle markers has provided valuable insight into various aspects of their cell biology, including invasion strategies in plant pathogenic fungi. Here, we introduce a set of 17 vectors that encode fluorescent markers to visualize the plasma membrane, endoplasmic reticulum (ER), chromosomes, the actin cytoskeleton, peroxisomes and autophagosomes in the wheat pathogen Zymoseptoria tritici...
August 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/28537477/atg-conjugation-dependent-degradation-of-the-inner-autophagosomal-membrane-is-a-key-step-for-autophagosome-maturation
#6
Ikuko Koyama-Honda, Kotaro Tsuboyama, Noboru Mizushima
Although the autophagy-related (ATG) conjugation systems are thought to be important for a late step of autophagosome formation, their precise function has been poorly understood because they are also required for localization of the most important autophagosomal marker LC3. In our recent study we found that, using the autophagosomal SNARE STX17 (syntaxin 17) as an alternative marker, autophagosome-like structures were generated in ATG conjugation system-deficient cells. Those structures could fuse with lysosomes but the degradation of the inner autophagosomal membrane was significantly delayed...
July 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28533369/phosphorylated-presenilin-1-decreases-%C3%AE-amyloid-by-facilitating-autophagosome-lysosome-fusion
#7
Victor Bustos, Maria V Pulina, Ashley Bispo, Alison Lam, Marc Flajolet, Fred S Gorelick, Paul Greengard
Presenilin 1 (PS1), the catalytic subunit of the γ-secretase complex, cleaves βCTF to produce Aβ. We have shown that PS1 regulates Aβ levels by a unique bifunctional mechanism. In addition to its known role as the catalytic subunit of the γ-secretase complex, selective phosphorylation of PS1 on Ser367 decreases Aβ levels by increasing βCTF degradation through autophagy. Here, we report the molecular mechanism by which PS1 modulates βCTF degradation. We show that PS1 phosphorylated at Ser367, but not nonphosphorylated PS1, interacts with Annexin A2, which, in turn, interacts with the lysosomal N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) Vamp8...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28504273/legionella-effector-lpg1137-shuts-down-er-mitochondria-communication-through-cleavage-of-syntaxin-17
#8
Kohei Arasaki, Yumi Mikami, Stephanie R Shames, Hiroki Inoue, Yuichi Wakana, Mitsuo Tagaya
During infection of macrophages, the pathogenic bacterium Legionella pneumophila secretes effector proteins that induce the conversion of the plasma membrane-derived vacuole into an endoplasmic reticulum (ER)-like replicative vacuole. These ER-like vacuoles are ultimately fused with the ER, where the pathogen replicates. Here we show that the L. pneumophila effector Lpg1137 is a serine protease that targets the mitochondria and their associated membranes. Lpg1137 binds to and cleaves syntaxin 17, a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein that is known to participate in the regulation of mitochondrial dynamics through interaction with the mitochondrial fission factor Drp1 in fed cells and in autophagy through interaction with Atg14L and other SNAREs in starved cells...
May 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/27932448/dedicated-snares-and-specialized-trim-cargo-receptors-mediate-secretory-autophagy
#9
Tomonori Kimura, Jingyue Jia, Suresh Kumar, Seong Won Choi, Yuexi Gu, Michal Mudd, Nicolas Dupont, Shanya Jiang, Ryan Peters, Farzin Farzam, Ashish Jain, Keith A Lidke, Christopher M Adams, Terje Johansen, Vojo Deretic
Autophagy is a process delivering cytoplasmic components to lysosomes for degradation. Autophagy may, however, play a role in unconventional secretion of leaderless cytosolic proteins. How secretory autophagy diverges from degradative autophagy remains unclear. Here we show that in response to lysosomal damage, the prototypical cytosolic secretory autophagy cargo IL-1β is recognized by specialized secretory autophagy cargo receptor TRIM16 and that this receptor interacts with the R-SNARE Sec22b to recruit cargo to the LC3-II(+) sequestration membranes...
January 4, 2017: EMBO Journal
https://www.readbyqxmd.com/read/27885029/the-atg-conjugation-systems-are-important-for-degradation-of-the-inner-autophagosomal-membrane
#10
Kotaro Tsuboyama, Ikuko Koyama-Honda, Yuriko Sakamaki, Masato Koike, Hideaki Morishita, Noboru Mizushima
In macroautophagy, cytoplasmic contents are sequestered into the double-membrane autophagosome, which fuses with the lysosome to become the autolysosome. It has been thought that the autophagy-related (ATG) conjugation systems are required for autophagosome formation. Here, we found that autophagosomal soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) syntaxin 17-positive autophagosome-like structures could be generated even in the absence of the ATG conjugation systems, although at a reduced rate...
November 25, 2016: Science
https://www.readbyqxmd.com/read/27701906/escrts-and-associated-proteins-in-lysosomal-fusion-with-endosomes-and-autophagosomes
#11
Priyanka Majumder, Oishee Chakrabarti
Endolysosomal and autophagosomal degradation pathways are highly connected at various levels, sharing multiple molecular effectors that modulate them individually or simultaneously. These two lysosomal degradative pathways are primarily involved in the disposal of cargo internalized from the cell surface or long-lived proteins or aggregates and aged organelles present in the cytosol. Both of these pathways involve a number of carefully regulated vesicular fusion events that are dependent on ESCRT proteins. The ESCRT proteins especially ESCRT-I and III participate in the regulation of fusion events between autophagosome/amphisome and lysosome...
July 22, 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/27646276/the-munc18-1-domain-3a-hinge-loop-controls-syntaxin-1a-nanodomain-assembly-and-engagement-with-the-snare-complex-during-secretory-vesicle-priming
#12
Ravikiran Kasula, Ye Jin Chai, Adekunle T Bademosi, Callista B Harper, Rachel S Gormal, Isabel C Morrow, Eric Hosy, Brett M Collins, Daniel Choquet, Andreas Papadopulos, Frédéric A Meunier
Munc18-1 and syntaxin-1A control SNARE-dependent neuroexocytosis and are organized in nanodomains on the plasma membrane of neurons and neurosecretory cells. Deciphering the intra- and intermolecular steps via which they prepare secretory vesicles (SVs) for fusion is key to understanding neuronal and hormonal communication. Here, we demonstrate that expression of a priming-deficient mutant lacking 17 residues of the domain 3a hinge-loop (Munc18-1(Δ317-333)) in PC12 cells engineered to knockdown Munc18-1/2 markedly prolonged SV docking...
September 26, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27628032/lamp-2-is-required-for-incorporating-syntaxin-17-into-autophagosomes-and-for-their-fusion-with-lysosomes
#13
Virginie Hubert, Andrea Peschel, Brigitte Langer, Marion Gröger, Andrew Rees, Renate Kain
Autophagy is an evolutionarily conserved process used for removing surplus and damaged proteins and organelles from the cytoplasm. The unwanted material is incorporated into autophagosomes that eventually fuse with lysosomes, leading to the degradation of their cargo. The fusion event is mediated by the interaction between the Qa-SNARE syntaxin-17 (STX17) on autophagosomes and the R-SNARE VAMP8 on lysosomes. Cells deficient in lysosome membrane-associated protein-2 (LAMP-2) have increased numbers of autophagosomes but the underlying mechanism is poorly understood...
October 15, 2016: Biology Open
https://www.readbyqxmd.com/read/27511942/ethylmercury-induced-oxidative-and-endoplasmic-reticulum-stress-mediated-autophagic-cell-death-involvement-of-autophagosome-lysosome-fusion-arrest
#14
Ji-Yoon Choi, Nam-Hee Won, Jung-Duck Park, Sinae Jang, Chi-Yong Eom, Yongseok Choi, Young In Park, Mi-Sook Dong
Ethylmercury (EtHg) is derived from the degradation of thimerosal, the most widely used organomercury compound. In this study, EtHg-induced toxicity and autophagy in the mouse kidney was observed and then the mechanism of toxicity was explored in vitro in HK-2 cells. Low doses of EtHg induced autophagy without causing any histopathological changes in mouse kidneys. However, mice treated with high doses of EtHg exhibited severe focal tubular cell necrosis of the proximal tubules with autophagy. EtHg dose-dependently increased the production of reactive oxygen species, reduced the mitochondrial membrane potential, activated the unfolded protein response, and increased cytosolic Ca(2+) levels in HK-2 cells...
August 10, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27458136/syntaxin-17-delivers-pink1-parkin-dependent-mitochondrial-vesicles-to-the-endolysosomal-system
#15
Gian-Luca McLelland, Sydney A Lee, Heidi M McBride, Edward A Fon
Mitochondria are considered autonomous organelles, physically separated from endocytic and biosynthetic pathways. However, recent work uncovered a PINK1/parkin-dependent vesicle transport pathway wherein oxidized or damaged mitochondrial content are selectively delivered to the late endosome/lysosome for degradation, providing evidence that mitochondria are indeed integrated within the endomembrane system. Given that mitochondria have not been shown to use canonical soluble NSF attachment protein receptor (SNARE) machinery for fusion, the mechanism by which mitochondrial-derived vesicles (MDVs) are targeted to the endosomal compartment has remained unclear...
August 1, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27458131/a-mitochondrial-derived-vesicle-hops-to-endolysosomes-using-syntaxin-17
#16
Gábor Juhász
Damaged mitochondrial content is packaged in mitochondrial-derived vesicles (MDVs), which are targeted for degradation through an unclear mechanism. McLelland et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201603105) show that the SNARE Syntaxin-17 mediates MDV fusion with endolysosomes, promoting the delivery of mitochondrial cargo to lysosomes for degradation.
August 1, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27270032/tetrandrine-induces-lipid-accumulation-through-blockade-of-autophagy-in-a-hepatic-stellate-cell-line
#17
Yusaku Miyamae, Yukina Nishito, Naomi Nakai, Yoko Nagumo, Takeo Usui, Seiji Masuda, Taiho Kambe, Masaya Nagao
Macroautophagy, or autophagy, is a cellular response in which unnecessary cytoplasmic components, including lipids and organelles, are self-degraded. Recent studies closely related autophagy to activation of hepatic stellate cells (HSCs), a process critical in the pathogenesis of liver fibrosis. During HSC activation, cytoplasmic lipid droplets (LDs) are degraded as autophagic cargo, and then cells express fibrogenic genes. Thus, inhibition of autophagy in HSCs is a potential therapeutic approach for attenuating liver fibrosis...
August 12, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27194408/inflammatory-insult-during-pregnancy-accelerates-age-related-behavioral-and-neurobiochemical-changes-in-cd-1-mice
#18
Xue-Yan Li, Fang Wang, Gui-Hai Chen, Xue-Wei Li, Qi-Gang Yang, Lei Cao, Wen-Wen Yan
Data shows that inflammation during pregnancy significantly exerts a long-term influence on offspring, such as increasing the risk of adult cognition decline in animals. However, it is unclear whether gestational inflammation affects the neurobehavioral and neurobiochemical outcomes in the mother-self during aging. In this study, pregnant CD-1 mice intraperitoneally received lipopolysaccharide (LPS) in two doses (25 and 50 g/kg, respectively) or normal saline daily during gestational days 15-17. At the age of 15 months, a battery of behavioral tasks was employed to evaluate their species-typical behaviors, sensorimotor ability, anxiety levels, and spatial learning and memory abilities...
June 2016: Age (2005-)
https://www.readbyqxmd.com/read/27099307/the-autophagosomal-snare-protein-syntaxin-17-is-an-essential-factor-for-the-hepatitis-c-virus-life-cycle
#19
Huimei Ren, Fabian Elgner, Bingfu Jiang, Kiyoshi Himmelsbach, Regina Medvedev, Daniela Ploen, Eberhard Hildt
UNLABELLED: Syntaxin 17 is an autophagosomal SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein required for the fusion of autophagosomes with lysosomes to form autolysosomes and thereby to deliver the enclosed contents for degradation. Hepatitis C virus (HCV) induces autophagy. In light of the observation that the number of viral particles formed by HCV-infected cells is much greater than the number of infectious viral particles finally released by HCV-infected cells, the regulation of fusion between autophagosomes and lysosomes might fulfill a key function controlling the number of released virions...
July 1, 2016: Journal of Virology
https://www.readbyqxmd.com/read/26911941/-suppressive-effect-of-exogenous-carbon-monoxide-on-abnormal-platelet-exocytosis-and-its-molecular-mechanism-in-sepsis
#20
Dadong Liu, Xiaohan Xu, Mingfeng Zhuang, Mingming Song, Weiting Qin, Xu Wang, Bingwei Sun
OBJECTIVE: To investigate the suppressive effect of exogenous carbon monoxide (CO) on abnormal platelet exocytosis and its possible molecular mechanism. METHODS: Venous blood was collected from healthy volunteers. Platelet-rich plasma (PRP) was isolated from the blood by differential centrifugation. The PRP was randomly divided into five groups by random number table, namely normal control group, lipopolysaccharide (LPS) group (challenged with 10 mg/L LPS), inactively exogenous carbon monoxide releasing molecule 2 (iCORM-2) group (given 10 mg/L LPS + 50 μmol/L iCORM-2 for intervention), exogenous carbon monoxide releasing molecule 2 (CORM-2) 10 μmol/L and 50 μmol/L groups (given 10 mg/L LPS + CORM-2 10 μmol/L or 50 μmol/L for intervention)...
February 2016: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
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