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Syntaxin 17

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...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
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
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
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
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
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
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
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
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
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. 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
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
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-)
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
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
Rong Rong, Hui Yang, Liangqun Rong, Xiue Wei, Qingjie Li, Xiaomei Liu, Hong Gao, Yun Xu, Qingxiu Zhang
Postsynaptic density protein-93 (PSD-93) is enriched in the postsynaptic density and is involved in N-methyl-d-aspartate receptor (NMDAR) triggered neurotoxicity through PSD-93/NMDAR/nNOS signaling pathway. In the present study, we found that PSD-93 deficiency reduced infarcted volume and neurological deficits induced by transient middle cerebral artery occlusion (tMCAO) in the mice. To identify novel targets of PSD-93 related neurotoxicity, we applied isobaric tags for relative and absolute quantitative (iTRAQ) labeling and combined this labeling with on-line two-dimensional LC/MS/MS technology to elucidate the changes in protein expression in PSD-93 knockout mice following tMCAO...
March 2016: Neurotoxicology
K X Gao, N B Chen, W J Liu, R Li, X Y Lan, H Chen, C Z Lei, R H Dang
Gray horses are born colored, and they then gradually lose their hair pigmentation. Tremendous progress has been made in identifying the genes responsible for graying with age in horses in recent years. Results show that gray coat color in horses is caused by a 4.6-kb duplication in intron 6 of the syntaxin 17 gene (STX17), which constitutes a cis-acting-regulatory mutation. However, little is known about the gray phenotype in native Chinese horses. This study was conducted to explore the frequency distribution of the gray mutation in native Chinese horse breeds...
2015: Genetics and Molecular Research: GMR
Yuanli Zhen, Wei Li
The HOPS (homotypic fusion and protein sorting) complex functions in endocytic and autophagic pathways in both lower eukaryotes and mammalian cells through its involvement in fusion events between endosomes and lysosomes or autophagosomes and lysosomes. However, the differential molecular mechanisms underlying these fusion processes are largely unknown. Buff (bf) is a mouse mutant that carries an Asp251-to-Glu point mutation (D251E) in the VPS33A protein, a tethering protein and a core subunit of the HOPS complex...
2015: Autophagy
Szabolcs Takáts, Ágnes Varga, Karolina Pircs, Gábor Juhász
The HOPS tethering complex facilitates autophagosome-lysosome fusion by binding to Syx17 (Syntaxin 17), the autophagosomal SNARE. Here we show that loss of the core HOPS complex subunit Vps16A enhances autophagosome formation and slows down Drosophila development. Mechanistically, Tor kinase is less active in Vps16A mutants likely due to impaired endocytic and biosynthetic transport to the lysosome, a site of its activation. Tor reactivation by overexpression of Rheb suppresses autophagosome formation and restores growth and developmental timing in these animals...
2015: Autophagy
Amélie Bernard, Daniel J Klionsky
Although largely overlooked relative to the process of phagophore formation, the mechanism through which autophagosomes fuse with lysosomes is a critical aspect of macroautophagy that is not fully understood. In particular, this step must be carefully regulated to prevent premature fusion of an incomplete autophagosome (that is, a phagophore) with a lysosome, because such an event would not allow access of the partially sequestered cargo to the lysosome lumen. The identification of the autophagosome-associated SNARE protein STX17 (syntaxin 17) provided some clue in the understanding of this process...
April 3, 2015: Autophagy
Jiajie Diao, Rong Liu, Yueguang Rong, Minglei Zhao, Jing Zhang, Ying Lai, Qiangjun Zhou, Livia M Wilz, Jianxu Li, Sandro Vivona, Richard A Pfuetzner, Axel T Brunger, Qing Zhong
Autophagy, an important catabolic pathway implicated in a broad spectrum of human diseases, begins by forming double membrane autophagosomes that engulf cytosolic cargo and ends by fusing autophagosomes with lysosomes for degradation. Membrane fusion activity is required for early biogenesis of autophagosomes and late degradation in lysosomes. However, the key regulatory mechanisms of autophagic membrane tethering and fusion remain largely unknown. Here we report that ATG14 (also known as beclin-1-associated autophagy-related key regulator (Barkor) or ATG14L), an essential autophagy-specific regulator of the class III phosphatidylinositol 3-kinase complex, promotes membrane tethering of protein-free liposomes, and enhances hemifusion and full fusion of proteoliposomes reconstituted with the target (t)-SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) syntaxin 17 (STX17) and SNAP29, and the vesicle (v)-SNARE VAMP8 (vesicle-associated membrane protein 8)...
April 23, 2015: Nature
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