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https://www.readbyqxmd.com/read/29789439/autophagosomal-ykt6-is-required-for-fusion-with-lysosomes-independently-of-syntaxin-17
#1
Takahide Matsui, Peidu Jiang, Saori Nakano, Yuriko Sakamaki, Hayashi Yamamoto, Noboru Mizushima
Macroautophagy is an evolutionarily conserved catabolic mechanism that delivers intracellular constituents to lysosomes using autophagosomes. To achieve degradation, lysosomes must fuse with closed autophagosomes. We previously reported that the soluble N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein syntaxin (STX) 17 translocates to autophagosomes to mediate fusion with lysosomes. In this study, we report an additional mechanism. We found that autophagosome-lysosome fusion is retained to some extent even in STX17 knockout (KO) HeLa cells...
May 22, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29734780/cpkc%C3%AE-modulated-sequential-reactivation-of-mtor-inhibited-autophagic-flux-in-neurons-exposed-to-oxygen-glucose-deprivation-reperfusion
#2
Rongrong Hua, Song Han, Nan Zhang, Qingqing Dai, Ting Liu, Junfa Li
We have reported that conventional protein kinase Cγ (cPKCγ)-modulated neuron-specific autophagy improved the neurological outcome of mice following ischemic stroke through the Akt-mechanistic target of rapamycin (mTOR) pathway. However, its detailed molecular mechanism remains unclear. In this study, primary cortical neurons from postnatal one-day-old C57BL/6J cPKCγ wild-type ( cPKCγ +/+ ) and knockout ( cPKCγ −/− ) mice suffering oxygen glucose deprivation/reperfusion (OGD/R) were used to simulate ischemia/reperfusion injury in vitro...
May 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29549094/syntaxin-17-promotes-lipid-droplet-formation-by-regulating-the-distribution-of-acyl-coa-synthetase-3
#3
Hana Kimura, Kohei Arasaki, Yuki Ohsaki, Toyoshi Fujimoto, Takayuki Ohtomo, Junji Yamada, Mitsuo Tagaya
Lipid droplets (LDs) are ubiquitous organelles that contain neutral lipids and are surrounded by a phospholipid monolayer. How proteins specifically localize to the phospholipid monolayer of the LD surface has been a matter of extensive investigations. In the present study, we show that syntaxin 17 (Stx17), a soluble N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein whose expression in the liver is regulated by diet, participates in LD biogenesis by regulating the distribution of acyl-CoA synthetase (ACSL)3, a key enzyme for LD biogenesis that redistributes from the endoplasmic reticulum (ER) to LDs during LD formation...
May 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29507186/increased-o-glcnacylation-of-snap29-drives-arsenic-induced-autophagic-dysfunction
#4
Matthew Dodson, Pengfei Liu, Tao Jiang, Andrew J Ambrose, Gang Luo, Montserrat Rojo de la Vega, Aram B Cholanians, Pak Kin Wong, Eli Chapman, Donna D Zhang
Environmental exposure to arsenic is linked to adverse health effects including cancer and diabetes. Pleiotropic cellular effects are observed with arsenic exposure. Previously, we demonstrated that arsenic dysregulated the autophagy pathway at low, environmentally relevant concentrations. Here, we show that arsenic blocks autophagy by preventing autophagosome-lysosome fusion. Specifically, arsenic disrupts formation of the STX17-SNAP29-VAMP8 SNARE complex, where SNAP29 mediates vesicle fusion through bridging STX17-containing autophagosomes to VAMP8-bearing lysosomes...
March 5, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29445155/the-cytotoxicity-of-coxsackievirus-b3-is-associated-with-a-blockage-of-autophagic-flux-mediated-by-reduced-syntaxin-17-expression
#5
Lang Tian, Yeyi Yang, Chunyun Li, Jia Chen, Zhuoying Li, Xin Li, Shentang Li, Fang Wu, Zhangxue Hu, Zuocheng Yang
Coxsackievirus B3 (CVB3) is an important human pathogen linked to cardiac arrhythmias and acute heart failure. CVB3 infection has been reported to induce the formation of autophagosomes that support the viral replication in host cells. Interestingly, our study shows that the accumulation of autophagosomes during CVB3 infection is caused by a blockage of autophagosome-lysosome fusion rather than the induction of autophagosome biogenesis. Moreover, CVB3 decreases the transcription and translation of syntaxin 17 (STX17), a SNARE (soluble N-ethylmaleimide-sensitive factor activating protein receptor) protein involved in autophagosome-lysosome fusion...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29420192/mechanism-of-stx17-recruitment-to-autophagosomes-via-irgm-and-mammalian-atg8-proteins
#6
Suresh Kumar, Ashish Jain, Farzin Farzam, Jingyue Jia, Yuexi Gu, Seong Won Choi, Michal H Mudd, Aurore Claude-Taupin, Michael J Wester, Keith A Lidke, Tor-Erik Rusten, Vojo Deretic
Autophagy is a conserved eukaryotic process with metabolic, immune, and general homeostatic functions in mammalian cells. Mammalian autophagosomes fuse with lysosomes in a SNARE-driven process that includes syntaxin 17 (Stx17). How Stx17 translocates to autophagosomes is unknown. In this study, we show that the mechanism of Stx17 recruitment to autophagosomes in human cells entails the small guanosine triphosphatase IRGM. Stx17 directly interacts with IRGM, and efficient Stx17 recruitment to autophagosomes requires IRGM...
March 5, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29080678/genome-wide-microrna-analysis-implicates-mir-30b-d-in-the-etiology-of-alopecia-areata
#7
Aylar Tafazzoli, Andreas J Forstner, David Broadley, Andrea Hofmann, Silke Redler, Lynn Petukhova, Kathrin A Giehl, Roland Kruse, Bettina Blaumeiser, Markus Böhm, Marta Bertolini, Alfredo Rossi, Natalie Garcia Bartels, Gerhard Lutz, Hans Wolff, Ulrike Blume-Peytavi, Hermona Soreq, Angela M Christiano, Natalia V Botchkareva, Markus M Nöthen, Regina C Betz
Alopecia areata (AA) is one of the most common forms of human hair loss. Although genetic studies have implicated autoimmune processes in AA etiology, understanding of the etiopathogenesis is incomplete. Recent research has implicated microRNAs, a class of small noncoding RNAs, in diverse autoimmune diseases. To our knowledge, no study has investigated the role of microRNAs in AA. In this study, gene-based analyses were performed for microRNAs using data of the largest genome-wide association meta-analysis of AA to date...
March 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29073720/malat1-modulates-the-autophagy-of-retinoblastoma-cell-through-mir-124-mediated-stx17-regulation
#8
Jun Huang, Yuting Yang, Fang Fang, Ke Liu
The retinoblastoma is the most common intraocular malignant tumor in infants and children; it is one of the deadliest forms of cancer due to its limited sensitivity to chemotherapy and radiotherapy. In several cancers, chemoresistance is associated with autophagy induction. Non-coding RNAs, including long non-coding RNAs (lncRNA) and microRNAs (miRNAs) have been reported to regulate physiological activities of the cells, including proliferation, apoptosis, migration, as well as autophagy. MALAT1, a well-established lncRNA acts as an oncogene, promotes cancer proliferation, and metastasis via the stimulation of autophagy...
May 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28933649/legionella-blocks-autophagy-by-cleaving-stx17-syntaxin-17
#9
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...
2017: Autophagy
https://www.readbyqxmd.com/read/28825857/borc-coordinates-encounter-and-fusion-of-lysosomes-with-autophagosomes
#10
Rui Jia, Carlos M Guardia, Jing Pu, Yu Chen, Juan S Bonifacino
Whereas the mechanisms involved in autophagosome formation have been extensively studied for the past 2 decades, those responsible for autophagosome-lysosome fusion have only recently begun to garner attention. In this study, we report that the multisubunit BORC complex, previously implicated in kinesin-dependent movement of lysosomes toward the cell periphery, is required for efficient autophagosome-lysosome fusion. Knockout (KO) of BORC subunits causes not only juxtanuclear clustering of lysosomes, but also increased levels of the autophagy protein LC3B-II and the receptor SQSTM1...
October 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28677644/2bc-non-structural-protein-of-enterovirus-a71-interacts-with-snare-proteins-to-trigger-autolysosome-formation
#11
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/28598244/accumulation-of-undegraded-autophagosomes-by-expression-of-dominant-negative-stx17-syntaxin-17-mutants
#12
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/28537477/atg-conjugation-dependent-degradation-of-the-inner-autophagosomal-membrane-is-a-key-step-for-autophagosome-maturation
#13
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/28368721/cellular-and-molecular-mechanism-for-secretory-autophagy
#14
Tomonori Kimura, Jingyue Jia, Aurore Claude-Taupin, 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
Macroautophagy/autophagy plays a role in unconventional secretion of leaderless cytosolic proteins. Whether and how secretory autophagy diverges from conventional degradative autophagy is unclear. We have shown that the prototypical secretory autophagy cargo IL1B/IL-1β (interleukin 1 β) is recognized by TRIM16, and that this first to be identified secretory autophagy receptor interacts with the R-SNARE SEC22B to jointly deliver cargo to the MAP1LC3B-II-positive sequestration membranes. Cargo secretion is unaffected by knockdowns of STX17, a SNARE catalyzing autophagosome-lysosome fusion as a prelude to cargo degradation...
June 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28306502/pacer-mediates-the-function-of-class-iii-pi3k-and-hops-complexes-in-autophagosome-maturation-by-engaging-stx17
#15
Xiawei Cheng, Xiuling Ma, Xianming Ding, Lin Li, Xiao Jiang, Zhirong Shen, She Chen, Wei Liu, Weihua Gong, Qiming Sun
Class III PI3-kinase (PI3KC3) is essential for autophagy initiation, but whether PI3KC3 participates in other steps of autophagy remains unknown. The HOPS complex mediates the fusion of intracellular vesicles to lysosome, but how HOPS specifically tethers autophagosome to lysosome remains elusive. Here, we report Pacer (protein associated with UVRAG as autophagy enhancer) as a regulator of autophagy. Pacer localizes to autophagic structures and positively regulates autophagosome maturation. Mechanistically, Pacer antagonizes Rubicon to stimulate Vps34 kinase activity...
March 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28253086/oocyte-developmental-competence-insights-from-cross-species-differential-gene-expression-and-human-oocyte-specific-functional-gene-networks
#16
Fernando H Biase
Understanding oocyte developmental competence remains a key challenge for reproductive biology and systems sciences. The transcriptome of oocytes in eutherians is highly complex and is associated with the success of embryo development. Due to sample limitations from humans, animal models are used for investigation of the oocyte transcriptome. Nonetheless, little is known about the diversity of the oocyte transcriptome across eutherians. In this report, comprehensive investigation of 7 public data sets in 4 species, human, macaque, mice, and cattle, shows that 16,572 genes are expressed in oocytes...
March 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/27628032/lamp-2-is-required-for-incorporating-syntaxin-17-into-autophagosomes-and-for-their-fusion-with-lysosomes
#17
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/27588602/the-vici-syndrome-protein-epg5-is-a-rab7-effector-that-determines-the-fusion-specificity-of-autophagosomes-with-late-endosomes-lysosomes
#18
Zheng Wang, Guangyan Miao, Xue Xue, Xiangyang Guo, Chongzhen Yuan, Zhaoyu Wang, Gangming Zhang, Yingyu Chen, Du Feng, Junjie Hu, Hong Zhang
Mutations in the human autophagy gene EPG5 cause the multisystem disorder Vici syndrome. Here we demonstrated that EPG5 is a Rab7 effector that determines the fusion specificity of autophagosomes with late endosomes/lysosomes. EPG5 is recruited to late endosomes/lysosomes by direct interaction with Rab7 and the late endosomal/lysosomal R-SNARE VAMP7/8. EPG5 also binds to LC3/LGG-1 (mammalian and C. elegans Atg8 homolog, respectively) and to assembled STX17-SNAP29 Qabc SNARE complexes on autophagosomes. EPG5 stabilizes and facilitates the assembly of STX17-SNAP29-VAMP7/8 trans-SNARE complexes, and promotes STX17-SNAP29-VAMP7-mediated fusion of reconstituted proteoliposomes...
September 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27511942/from-the-cover-ethylmercury-induced-oxidative-and-endoplasmic-reticulum-stress-mediated-autophagic-cell-death-involvement-of-autophagosome-lysosome-fusion-arrest
#19
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 Ca2+  levels in HK-2 cells...
November 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27490928/tmem166-eva1a-interacts-with-atg16l1-and-induces-autophagosome-formation-and-cell-death
#20
Jia Hu, Ge Li, Liujing Qu, Ning Li, Wei Liu, Dan Xia, Beiqi Hongdu, Xin Lin, Chentong Xu, Yaxin Lou, Qihua He, Dalong Ma, Yingyu Chen
The formation of the autophagosome is controlled by an orderly action of ATG proteins. However, how these proteins are recruited to autophagic membranes remain poorly clarified. In this study, we have provided a line of evidence confirming that EVA1A (eva-1 homolog A)/TMEM166 (transmembrane protein 166) is associated with autophagosomal membrane development. This notion is based on dotted EVA1A structures that colocalize with ZFYVE1, ATG9, LC3B, ATG16L1, ATG5, STX17, RAB7 and LAMP1, which represent different stages of the autophagic process...
August 4, 2016: Cell Death & Disease
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