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https://www.readbyqxmd.com/read/28426820/the-influence-of-cell-membrane-and-snap25-linker-loop-on-the-dynamics-and-unzipping-of-snare-complex
#1
Yi Shi, Yong Zhang, Jizhong Lou
The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex is composed of three neuronal proteins VAMP2, Syntaxin and SNAP25, which plays a core role during the process of membrane fusion. The zipping assembly of the SNARE complex releases energies and drives the vesicle and cell membrane into close proximity. In this study, we use all-atom molecular dynamics simulations to probe the dynamics of SNARE and its unzipping process in the context of membrane at the atomistic details...
2017: PloS One
https://www.readbyqxmd.com/read/28398146/protective-action-of-b1r-antagonist-against-cerebral-ischemia-reperfusion-injury-through-suppressing-mir-200c-expression-of-microglia-derived-microvesicles
#2
Min Tang, Ping Liu, Xia Li, Jian-Wen Wang, Xiong-Chao Zhu, Fang-Ping He
BACKGROUND AND OBJECTIVE: Cerebral ischemia-reperfusion (I/R) injury is a common side-effect for cerebral ischemic disease and its therapeutic regimen is limited. Kinin is pro-inflammatory peptide that is released and acts at the site of injury and inflammation such as brain and it works through bradykinin 1 receptor (B1R). The present study was to examine the effect of B1R antagonist on cerebral I/R injury and the potential mechanism. METHODS: Cerebral I/R injury was induced in mice by transient middle cerebral artery occlusion (MCAO)...
April 11, 2017: Neurological Research
https://www.readbyqxmd.com/read/28396819/rab11-fip1-phosphorylation-by-mark2-regulates-polarity-in-mdck-cells
#3
Rebecca McRae, Lynne A Lapierre, Elizabeth H Manning, James R Goldenring
MARK2/Par1b/EMK1, a serine/threonine kinase, is required for correct apical/basolateral membrane polarization in epithelial cells. However, the specific substrates mediating MARK2 action are less well understood. We have now found that MARK2 phosphorylates Rab11-FIP1B/C at serine 234 in a consensus site similar to that previously identified in Rab11-FIP2. In MDCK cells undergoing repolarization after a calcium switch, antibodies specific for pS234-Rab11-FIP1 or pS227-Rab11-FIP2 demonstrate that the spatial and temporal activation of Rab11-FIP1 phosphorylation is distinct from that for Rab11-FIP2...
2017: Cellular Logistics
https://www.readbyqxmd.com/read/28392696/compound-porcine-cerebroside-and-ganglioside-injection-attenuates-cerebral-ischemia-reperfusion-injury-in-rats-by-targeting-multiple-cellular-processes
#4
Mingyang Wang, Yi Zhang, Lu Feng, Ji Zheng, Shujie Fan, Junya Liu, Nan Yang, Yanyong Liu, Pingping Zuo
BACKGROUND: Compound porcine cerebroside and ganglioside injection (CPCGI) is a neurotrophic drug used clinically to treat certain functional disorders of brain. Despite its extensive usage throughout China, the exact mechanistic targets of CPCGI are unknown. This study was carried out to investigate the protective effect of CPCGI against ischemic neuronal damage in rats with middle cerebral artery occlusion (MCAO) reperfusion injury and to investigate the neuroprotective mechanisms of CPCGI...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28391067/n-type-ca-2-channels-are-affected-by-full-length-mutant-huntingtin-expression-in-a-mouse-model-of-huntington-s-disease
#5
Flavia R Silva, Artur S Miranda, Rebeca P M Santos, Isabella G Olmo, Gerald W Zamponi, Tomas Dobransky, Jader S Cruz, Luciene B Vieira, Fabiola M Ribeiro
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a polyglutamine expansion in the amino-terminal region of the huntingtin (htt) protein. In addition to facilitating neurodegeneration, mutant htt is implicated in HD-related alterations of neurotransmission. Previous data showed that htt can modulate N-type voltage-gated Ca(2+) channels (Cav2.2), which are essential for presynaptic neurotransmitter release. Thus, to elucidate the mechanism underlying mutant htt-mediated alterations in neurotransmission, we investigated how Cav2...
March 18, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28381425/an-endosomal-syntaxin-and-the-ap-3-complex-are-required-for-formation-and-maturation-of-candidate-lysosome-related-secretory-organelles-mucocysts-in-tetrahymena-thermophila
#6
Harsimran Kaur, Daniela Sparvoli, Hiroko Osakada, Masaaki Iwamoto, Tokuko Haraguchi, Aaron P Turkewitz
The ciliate Tetrahymena thermophila synthesizes large secretory vesicles called mucocysts. Mucocyst biosynthesis shares features with dense core granules (DCGs) in animal cells, including proteolytic processing of cargo proteins during maturation. However, other molecular features have suggested relatedness to lysosome-related organelles (LROs). LROs, which include diverse organelles in animals, are formed via convergence of secretory and endocytic trafficking. Here we analyzed Tetrahymena Stx7l1p (syntaxin 7-like 1), a Qa SNARE whose homologs in other lineages are linked with vacuoles/LROs...
April 5, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28368721/cellular-and-molecular-mechanism-for-secretory-autophagy
#7
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...
April 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28367336/evidence-of-presynaptic-localization-and-function-of-the-c-jun-n-terminal-kinase
#8
Silvia Biggi, Lucia Buccarello, Alessandra Sclip, Pellegrino Lippiello, Noemi Tonna, Cristiano Rumio, Daniele Di Marino, Maria Concetta Miniaci, Tiziana Borsello
The c-Jun N-terminal kinase (JNK) is part of a stress signalling pathway strongly activated by NMDA-stimulation and involved in synaptic plasticity. Many studies have been focused on the post-synaptic mechanism of JNK action, and less is known about JNK presynaptic localization and its physiological role at this site. Here we examined whether JNK is present at the presynaptic site and its activity after presynaptic NMDA receptors stimulation. By using N-SIM Structured Super Resolution Microscopy as well as biochemical approaches, we demonstrated that presynaptic fractions contained significant amount of JNK protein and its activated form...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28348516/molecular-mechanisms-for-the-coupling-of-endocytosis-to-exocytosis-in-neurons
#9
REVIEW
Zhenli Xie, Jiangang Long, Jiankang Liu, Zuying Chai, Xinjiang Kang, Changhe Wang
Neuronal communication and brain function mainly depend on the fundamental biological events of neurotransmission, including the exocytosis of presynaptic vesicles (SVs) for neurotransmitter release and the subsequent endocytosis for SV retrieval. Neurotransmitters are released through the Ca(2+)- and SNARE-dependent fusion of SVs with the presynaptic plasma membrane. Following exocytosis, endocytosis occurs immediately to retrieve SV membrane and fusion machinery for local recycling and thus maintain the homeostasis of synaptic structure and sustained neurotransmission...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28348137/early-golgi-abnormalities-and-neurodegeneration-upon-loss-of-presynaptic-proteins-munc18-1-syntaxin-1-or-snap-25
#10
Tatiana C Santos, Keimpe Wierda, Jurjen H Broeke, Ruud F Toonen, Matthijs Verhage
The loss of presynaptic proteins Munc18-1, syntaxin-1 or SNAP-25 is known to produce cell death, but the underlying features have not been compared experimentally. Here, we investigated these features in cultured mouse CNS and dorsal root ganglion neurons. Side-by-side comparisons confirmed massive cell death, before synaptogenesis, within 1-4 days in vitro (DIV) upon loss of t-SNAREs (syntaxin-1, SNAP-25) or Munc18-1, but not v-SNAREs (synaptobrevins/VAMP1/2/3 using Tetanus Neurotoxin (TeNT), also in TI-VAMP/VAMP7 knock-out (KO) neurons)...
March 27, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28325894/sumoylation-and-calcium-control-syntaxin-1a-and-secretagogin-sequestration-by-tomosyn-to-regulate-insulin-exocytosis-in-human-%C3%A3-cells
#11
Mourad Ferdaoussi, Jianyang Fu, Xiaoqing Dai, Jocelyn E Manning Fox, Kunimasa Suzuki, Nancy Smith, Gregory Plummer, Patrick E MacDonald
Insulin secretion from pancreatic ß cells is a multistep process that requires the coordination of exocytotic proteins that integrate diverse signals. These include signals derived from metabolic control of post-translational SUMOylation and depolarization-induced rises in intracellular Ca(2+). Here we show that tomosyn, which suppresses insulin exocytosis by binding syntaxin1A, does so in a manner which requires its SUMOylation. Glucose-dependent de-SUMOylation of tomosyn1 at K298 releases syntaxin1A and controls the amplification of exocytosis in concert with a recently-identified tomosyn1-interacting partner; the Ca(2+)-binding protein secretagogin, which dissociates from tomosyn1 in response to Ca(2+)-raising stimuli and is required for insulin granule trafficking and exocytosis downstream of Ca(2+) influx...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28314963/mir-124a-expression-contributes-to-the-monophasic-pattern-of-insulin-secretion-in-islets-from-pregnant-rats-submitted-to-a-low-protein-diet
#12
Kariny Cassia de Siqueira, Faena Moura de Lima, Fernanda Souza Lima, Marina Satie Taki, Clarissa Felfili da Cunha, Sílvia Regina de Lima Reis, Rafael Ludemann Camargo, Thiago Martins Batista, Emerielle Cristine Vanzela, Tarlliza Romanna Nardelli, Everardo Magalhães Carneiro, Silvana Bordin, Letícia Martins Ignácio-Souza, Márcia Queiroz Latorraca
PURPOSE: To evaluate the role of miR-124a in the regulation of genes involved in insulin exocytosis and its effects on the kinetics of insulin secretion in pancreatic islets from pregnant rats submitted to a low-protein diet. METHODS: Adult control non-pregnant (CNP) and control pregnant (CP) rats were fed a normal protein diet (17%), whereas low-protein non-pregnant (LPNP) and low-protein pregnant (LPP) rats were fed a low-protein diet (6%) from days 1 to 15 of pregnancy...
March 17, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28265073/sm-protein-munc18-2-facilitates-transition-of-syntaxin-11-mediated-lipid-mixing-to-complete-fusion-for-t-lymphocyte-cytotoxicity
#13
Waldo A Spessott, Maria L Sanmillan, Margaret E McCormick, Vineet V Kulkarni, Claudio G Giraudo
The atypical lipid-anchored Syntaxin 11 (STX11) and its binding partner, the Sec/Munc (SM) protein Munc18-2, facilitate cytolytic granule release by cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Patients carrying mutations in these genes develop familial hemophagocytic lymphohistiocytosis, a primary immunodeficiency characterized by impaired lytic granule exocytosis. However, whether a SNARE such as STX11, which lacks a transmembrane domain, can support membrane fusion in vivo is uncertain, as is the precise role of Munc18-2 during lytic granule exocytosis...
March 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28202687/oxidized-phagosomal-nox2-complex-is-replenished-from-lysosomes
#14
Ilse Dingjan, Peter T A Linders, Luuk van den Bekerom, Maksim V Baranov, Partho Halder, Martin Ter Beest, Geert van den Bogaart
In dendritic cells, the NADPH oxidase 2 complex (NOX2) is recruited to the phagosomal membrane during antigen uptake. NOX2 produces reactive oxygen species (ROS) in the lumen of the phagosome that kill ingested pathogens, delay antigen breakdown and alter the peptide repertoire for presentation to T cells. How the integral membrane component of NOX2, cytochrome b558 (which comprises CYBB and CYBA), traffics to phagosomes is incompletely understood. In this study, we show in dendritic cells derived from human blood-isolated monocytes that cytochrome b558 is initially recruited to the phagosome from the plasma membrane during phagosome formation...
April 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28202235/stx12-lncrna-mir-148a-smad5-participate-in-the-regulation-of-pancreatic-stellate-cell-activation-through-a-mechanism-involving-competing-endogenous-rna
#15
Hao Wang, Yanfeng Jiang, Ming Lu, Bei Sun, Xin Qiao, Dongbo Xue, Weihui Zhang
BACKGROUND: With the deepening of research, the roles of LncRNAs play in the fibrotic process have attracted great attention. At the early stage of pancreatic fibrogenesis, to effectively regulate pancreatic stellate cells (PSCs) activation is crucial for the treatment of chronic pancreatic fibrosis. METHODS: Microarray data on chronic pancreatitis were retrieved from the Gene Expression Omnibus (GEO) repository and analyzed using bioinformatic methods. A diagram of the lncRNA-miRNA-mRNA ceRNA network was constructed...
February 1, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28163686/the-multifaceted-role-of-snare-proteins-in-membrane-fusion
#16
REVIEW
Jing Han, Kristyna Pluhackova, Rainer A Böckmann
Membrane fusion is a key process in all living organisms that contributes to a variety of biological processes including viral infection, cell fertilization, as well as intracellular transport, and neurotransmitter release. In particular, the various membrane-enclosed compartments in eukaryotic cells need to exchange their contents and communicate across membranes. Efficient and controllable fusion of biological membranes is known to be driven by cooperative action of SNARE proteins, which constitute the central components of the eukaryotic fusion machinery responsible for fusion of synaptic vesicles with the plasma membrane...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28163042/munc18b-increases-insulin-granule-fusion-restoring-deficient-insulin-secretion-in-type-2-diabetes-human-and-goto-kakizaki-rat-islets-with-improvement-in-glucose-homeostasis
#17
Tairan Qin, Tao Liang, Dan Zhu, Youhou Kang, Li Xie, Subhankar Dolai, Shuzo Sugita, Noriko Takahashi, Claes-Goran Ostenson, Kate Banks, Herbert Y Gaisano
Reduced pancreatic islet levels of Munc18a/SNARE complex proteins have been postulated to contribute to the deficient glucose-stimulated insulin secretion (GSIS) in type-2 diabetes (T2D). Whereas much previous work has purported Munc18a/SNARE complex (Syntaxin-1A/VAMP-2/SNAP25) to be primarily involved in predocked secretory granule (SG) fusion, less is known about newcomer SGs that undergo minimal docking time at the plasma membrane before fusion. Newcomer SG fusion has been postulated to involve a distinct SM/SNARE complex (Munc18b/Syntaxin-3/VAMP8/SNAP25), whose levels we find also reduced in islets of T2D humans and T2D Goto-Kakizaki (GK) rats...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28137749/conformational-change-of-syntaxin-linker-region-induced-by-munc13s-initiates-snare-complex-formation-in-synaptic-exocytosis
#18
Shen Wang, Ucheor B Choi, Jihong Gong, Xiaoyu Yang, Yun Li, Austin L Wang, Xiaofei Yang, Axel T Brunger, Cong Ma
The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein syntaxin-1 adopts a closed conformation when bound to Munc18-1, preventing binding to synaptobrevin-2 and SNAP-25 to form the ternary SNARE complex. Although it is known that the MUN domain of Munc13-1 catalyzes the transition from the Munc18-1/syntaxin-1 complex to the SNARE complex, the molecular mechanism is unclear. Here, we identified two conserved residues (R151, I155) in the syntaxin-1 linker region as key sites for the MUN domain interaction...
March 15, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28119011/syntaxin-4-and-snap23-act-as-exocytic-snares-to-release-ngf-from-cultured-schwann-cells
#19
Mengsi Lin, Maorong Jiang, Fei Ding, Zheng Cao
Nowadays peripheral nerve (PN) injury occurs more frequently, the outcome is often poor because of the ineffective treatment. Once the PN was injured, Schwann cells (SCs) release neurotrophins to guide the regeneration of axons. Recent researches revealed the duration of NGF administration acts a positive role during the nerve regeneration, but the molecular mechanisms of NGF release from SCs are unknown. To investigate components of the exocytic machinery of NGF, we used RT-PCR, Western blot and immunocytochemistry to investigate expressions and locations of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) in rat primary cultured SCs...
January 21, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28116546/cortical-synaptic-transmission-and-plasticity-in-acute-liver-failure-are-decreased-by-presynaptic-events
#20
Mariusz Popek, Bartosz Bobula, Joanna Sowa, Grzegorz Hess, Rafał Polowy, Robert Kuba Filipkowski, Małgorzata Frontczak-Baniewicz, Barbara Zabłocka, Jan Albrecht, Magdalena Zielińska
Neurological symptoms of acute liver failure (ALF) reflect decreased excitatory transmission, but the status of ALF-affected excitatory synapse has not been characterized in detail. We studied the effects of ALF in mouse on synaptic transmission and plasticity ex vivo and its relation to distribution of (i) synaptic vesicles (sv) and (ii) functional synaptic proteins within the synapse. ALF-competent neurological and biochemical changes were induced in mice with azoxymethane (AOM). Electrophysiological characteristics (long-term potentiation, whole-cell recording) as well as synapse ultrastructure were evaluated in the cerebral cortex...
January 23, 2017: Molecular Neurobiology
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