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https://www.readbyqxmd.com/read/29161591/cell-invasion-in%C3%A2-vivo-via-rapid-exocytosis-of-a-transient-lysosome-derived-membrane-domain
#1
Kaleb M Naegeli, Eric Hastie, Aastha Garde, Zheng Wang, Daniel P Keeley, Kacy L Gordon, Ariel M Pani, Laura C Kelley, Meghan A Morrissey, Qiuyi Chi, Bob Goldstein, David R Sherwood
Invasive cells use small invadopodia to breach basement membrane (BM), a dense matrix that encases tissues. Following the breach, a large protrusion forms to clear a path for tissue entry by poorly understood mechanisms. Using RNAi screening for defects in Caenorhabditis elegans anchor cell (AC) invasion, we found that UNC-6(netrin)/UNC-40(DCC) signaling at the BM breach site directs exocytosis of lysosomes using the exocyst and SNARE SNAP-29 to form a large protrusion that invades vulval tissue. Live-cell imaging revealed that the protrusion is enriched in the matrix metalloprotease ZMP-1 and transiently expands AC volume by more than 20%, displacing surrounding BM and vulval epithelium...
November 20, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29160768/diverse-modes-of-synaptic-signaling-regulation-and-plasticity-distinguish-classes-of-c-elegans-glutamatergic-neurons
#2
Donovan Ventimiglia, Cornelia I Bargmann
Synaptic vesicle release properties vary between neuronal cell types, but in most cases the molecular basis of this heterogeneity is unknown. Here, we compare in vivo synaptic properties of two neuronal classes in the C. elegans central nervous system, using VGLUT-pHluorin to monitor synaptic vesicle exocytosis and retrieval in intact animals. We show that the glutamatergic sensory neurons AWC(ON) and ASH have distinct synaptic dynamics associated with tonic and phasic synaptic properties, respectively. Exocytosis in ASH and AWC(ON) is differentially affected by SNARE-complex regulators that are present in both neurons: phasic ASH release is strongly dependent on UNC-13, whereas tonic AWC(ON) release relies upon UNC-18 and on the protein kinase C homolog PKC-1...
November 21, 2017: ELife
https://www.readbyqxmd.com/read/29158500/use-dependent-potentiation-of-voltage-gated-calcium-channels-rescues-neurotransmission-in-nerve-terminals-intoxicated-by-botulinum-neurotoxin-serotype-a
#3
Phillip H Beske, Katie M Hoffman, James B Machamer, Margaret R Eisen, Patrick M McNutt
Botulinum neurotoxins (BoNTs) are highly potent toxins that cleave neuronal SNARE proteins required for neurotransmission, causing flaccid paralysis and death by asphyxiation. Currently, there are no clinical treatments to delay or reverse BoNT-induced blockade of neuromuscular transmission. While aminopyridines have demonstrated varying efficacy in transiently reducing paralysis following BoNT poisoning, the precise mechanisms by which aminopyridines symptomatically treat botulism are not understood. Here we found that activity-dependent potentiation of presynaptic voltage-gated calcium channels (VGCCs) underlies 3,4-diaminopyridine (3,4-DAP)-mediated rescue of neurotransmission in central nervous system synapses and mouse diaphragm neuromuscular junctions fully intoxicated by BoNT serotype A...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29158178/dissection-enabled-scaffold-assisted-resection-descar-a-novel-technique-for-resection-of-residual-or-non-lifting-gi-neoplasia-of-the-colon-with-video
#4
Matthew W Stier, Christopher G Chapman, Allie Kreitman, John A Hart, Shu-Yuan Xiao, Uzma D Siddiqui, Irving Waxman
BACKGROUND AND AIMS: Due to previous manipulation or submucosal invasion, GI lesions referred for endoscopic mucosal resection (EMR) frequently have flat areas of visible tissue that cannot be snared. Current methods for treating residual tissue may lead to incomplete eradication or not allow complete tissue sampling for histologic evaluation. Our aim is to describe dissection-enabled scaffold-assisted resection (DeSCAR), a new technique combining circumferential ESD with EMR for removal of superficial non-lifting or residual "islands" with suspected submucosal involvement/fibrosis...
November 17, 2017: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/29150433/tyrosine-phosphorylation-of-munc18-1-inhibits-synaptic-transmission-by-preventing-snare%C3%A2-assembly
#5
Marieke Meijer, Bernhard Dörr, Hanna Ca Lammertse, Chrysanthi Blithikioti, Jan Rt van Weering, Ruud Fg Toonen, Thomas H Söllner, Matthijs Verhage
Tyrosine kinases are important regulators of synaptic strength. Here, we describe a key component of the synaptic vesicle release machinery, Munc18-1, as a phosphorylation target for neuronal Src family kinases (SFKs). Phosphomimetic Y473D mutation of a SFK phosphorylation site previously identified by brain phospho-proteomics abolished the stimulatory effect of Munc18-1 on SNARE complex formation ("SNARE-templating") and membrane fusion in vitro Furthermore, priming but not docking of synaptic vesicles was disrupted in hippocampal munc18-1-null neurons expressing Munc18-1Y473D Synaptic transmission was temporarily restored by high-frequency stimulation, as well as by a Munc18-1 mutation that results in helix 12 extension, a critical conformational step in vesicle priming...
November 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29148542/prrt2-dependent-dyskinesia-cerebellar-paroxysmal-and-persistent
#6
Lieke Kros, Chris I De Zeeuw
In an elegant publication in Cell Research, Tan and colleagues showed that ablation of PRRT2 in cerebellar granule cells is sufficient to induce paroxysmal kinesigenic dyskinesia. PRRT2 turns out to downregulate the presynaptic SNARE complex in granule cell axons, which in turn controls the activity patterns of Purkinje cells, the sole output of the cerebellar cortex.
November 17, 2017: Cell Research
https://www.readbyqxmd.com/read/29145243/obstructive-internal-hernia-caused-by-mesodiverticular-bands-in-children-two-case-reports-and-a-review-of-the-literature
#7
Mirko Bertozzi, Berardino Melissa, Elisa Magrini, Giuseppe Di Cara, Susanna Esposito, Antonino Apignani
INTRODUCTION: The mesodiverticular band (MDB) is an embryologic remnant of the vitelline circulation, which carries the arterial supply to the Meckel diverticulum. In the event of an error of involution, a patent or nonpatent arterial band persists and extends from the mesentery to the apex of the antimesenteric diverticulum. This creates a snare-like opening through which bowel loops may herniate and become obstructed. This report describes 2 rare cases of small bowel occlusion owing to an internal hernia caused by a MDB...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29139159/syntaxin1b-contributes-to-regulation-of-the-dopaminergic-system-through-gaba-transmission-in-the-cns
#8
Tomonori Fujiwara, Takefumi Kofuji, Tatsuya Mishima, Kimio Akagawa
In neuronal plasma membrane, two syntaxin isoforms, HPC-1/syntaxin1A (STX1A) and syntaxin1B (STX1B), are predominantly expressed as soluble N-ethylmaleimide-sensitive fusion attachment protein receptors, also known as t-SNAREs. We previously reported that glutamatergic and GABAergic synaptic transmission is impaired in Stx1b null mutant (Stx1b(-/-) ) mice, but is almost normal in Stx1a null mutant (Stx1a(-/-) ) mice. These observations suggested that STX1A and STX1B have distinct functions in fast synaptic transmission in the central nervous system (CNS)...
November 15, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29138318/snare-priming-is-essential-for-maturation-of-autophagosomes-but-not-for-their-formation
#9
Adi Abada, Smadar Levin-Zaidman, Ziv Porat, Tali Dadosh, Zvulun Elazar
Autophagy, a unique intracellular membrane-trafficking pathway, is initiated by the formation of an isolation membrane (phagophore) that engulfs cytoplasmic constituents, leading to generation of the autophagosome, a double-membrane vesicle, which is targeted to the lysosome. The outer autophagosomal membrane consequently fuses with the lysosomal membrane. Multiple membrane-fusion events mediated by SNARE molecules have been postulated to promote autophagy. αSNAP, the adaptor molecule for the SNARE-priming enzyme N-ethylmaleimide-sensitive factor (NSF) is known to be crucial for intracellular membrane fusion processes, but its role in autophagy remains unclear...
November 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29137486/the-arteriolar-glycocalyx-plays-a-role-in-the-regulation-of-blood-flow-in-the-iliac-of-the-anaesthetised-pig
#10
T Ruane-O'Hora, F Markos
The role of the glycocalyx of arterial resistance vessels in regulating blood flow in vivo is not fully understood. Therefore, the effect of glycocalyx damage using two separate compounds, hyaluronidase and N-Formylmethionyl-leucyl-phenylalanine (fMLP), was evaluated in the iliac artery vascular bed of the anaesthetised pig. Blood flow and pressure were measured in the iliac, an adjustable snare was applied to the iliac above the pressure and flow measurement site to induce step decreases (3 occlusions at 3-4 min intervals were performed for each infusion) in blood flow, and hence iliac pressure, and vascular conductance (flow / pressure) was calculated...
November 10, 2017: Physiological Research
https://www.readbyqxmd.com/read/29135058/distinct-features-of-multivesicular-body-lysosome-fusion-revealed-by-a-new-cell-free-content-mixing-assay
#11
Mahmoud Abdul Karim, Dieter Ronny Samyn, Sevan Mattie, Christopher Leonard Brett
When marked for degradation, surface receptor and transporter proteins are internalized and delivered to endosomes where they are packaged into intralumenal vesicles (ILVs). Many rounds of ILV formation create multivesicular bodies (MVBs) that fuse with lysosomes exposing ILVs to hydrolases for catabolism. Despite being critical for protein degradation, the molecular underpinnings of MVB-lysosome fusion remain unclear, although machinery underlying other lysosome fusion events is implicated. But how then is specificity conferred? And how is MVB maturation and fusion coordinated for efficient protein degradation? To address these questions, we developed a cell-free MVB-lysosome fusion assay using S...
November 14, 2017: Traffic
https://www.readbyqxmd.com/read/29133430/the-dual-function-of-the-polybasic-juxtamembrane-region-of-syntaxin-1a-in-clamping-spontaneous-release-and-stimulating-ca-2-triggered-release-in-neuroendocrine-cells
#12
Dafna Singer-Lahat, Noa Barak-Broner, Anton Sheinin, Dafna Greitzer-Antes, Izhak Michaelevski, Ilana Lotan
The exact function of the polybasic juxtamembrane region (5RK) of the plasma membrane neuronal SNARE, syntaxin 1A (Syx), in vesicle exocytosis, although widely studied, is currently not clear. Here, we addressed the role of 5RK in Ca(2+)-triggered release, using our Syx-based intramolecular FRET probe, which previously allowed us to resolve a depolarization-induced Ca(+2)- dependent close-to-open transition (CDO) of Syx that occurs concomitant with evoked release, both in PC12 cells and hippocampal neurons and was abolished upon charge neutralization of 5RK...
November 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29133196/cold-endoscopic-mucosal-resection-of-large-sessile-serrated-polyps-at-colonoscopy-with-video
#13
Nicholas J Tutticci, David G Hewett
BACKGROUND AND AIMS: The optimal technique for the resection of sessile serrated polyps (SSPs) is unknown, with established limitations and risks with conventional polypectomy. Although cold snare polypectomy is safe, the efficacy of piecemeal resection for large lesions is untested. In this study, we evaluate the safety and efficacy of cold endoscopic mucosal resection (EMR) for large SSPs. METHODS: Patients presenting for elective colonoscopy at an academic endoscopy center with 1 or more SSPs ≥10mm in size were enrolled, excluding those on anticoagulants or antiplatelets other than aspirin...
November 10, 2017: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/29130426/nupr1-maintains-autolysosomal-efflux-by-activating-snap25-transcription-in-cancer-cells
#14
Yanchao Mu, Xiaojie Yan, Ding Li, Dan Zhao, Lingling Wang, Xiaoyang Wang, Dan Gao, Jie Yang, Hua Zhang, Yanzhe Li, Yanan Sun, Yiliang Wei, Zhenfa Zhang, Xinzhong Chang, Zhi Yao, Shanshan Tian, Kai Zhang, Lance S Terada, Zhenyi Ma, Zhe Liu
In the advanced stages of cancer, autophagy is thought to promote tumor progression through its ability to mitigate various cellular stresses. However, the details of how autophagy is homeostatically regulated in such tumors are unknown. Here, we report that NUPR1 (nuclear protein 1, transcriptional regulator), a transcriptional coregulator, is aberrantly expressed in a subset of cancer cells and predicts low overall survival rates for lung cancer patients. NUPR1 regulates the late stages of autolysosome processing through the induction of the SNARE protein SNAP25, which forms a complex with the lysosomal SNARE-associated protein VAMP8...
November 13, 2017: Autophagy
https://www.readbyqxmd.com/read/29129207/fusion-pore-in-exocytosis-more-than-an-exit-gate-a-%C3%AE-cell-perspective
#15
REVIEW
Benoit Hastoy, Anne Clark, Patrik Rorsman, Jochen Lang
Secretory vesicle exocytosis is a fundamental biological event and the process by which hormones (like insulin) are released into the blood. Considerable progress has been made in understanding this precisely orchestrated sequence of events from secretory vesicle docked at the cell membrane, hemifusion, to the opening of a membrane fusion pore. The exact biophysical and physiological regulation of these events implies a close interaction between membrane proteins and lipids in a confined space and constrained geometry to ensure appropriate delivery of cargo...
December 2017: Cell Calcium
https://www.readbyqxmd.com/read/29127297/rab5-is-critical-for-snap23-regulated-granule-granule-fusion-during-compound-exocytosis
#16
Ofir Klein, Amit Roded, Neta Zur, Nurit P Azouz, Olga Pasternak, Koret Hirschberg, Ilan Hammel, Paul A Roche, Ayaka Yatsu, Mitsunori Fukuda, Stephen J Galli, Ronit Sagi-Eisenberg
Compound exocytosis is considered the most massive mode of exocytosis, during which the membranes of secretory granules (SGs) fuse with each other to form a channel through which the entire contents of their granules is released. The underlying mechanisms of compound exocytosis remain largely unresolved. Here we show that the small GTPase Rab5, a known regulator of endocytosis, is pivotal for compound exocytosis in mast cells. Silencing of Rab5 shifts receptor-triggered secretion from a compound to a full exocytosis mode, in which SGs individually fuse with the plasma membrane...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29125213/gastrointestinal-spray-coagulation-with-snare-tip-as-a-rescue-therapy-to-argon-plasma-coagulation-for-bleeding-jejunal-angioectasia
#17
H H Yen
No abstract text is available yet for this article.
December 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29122600/width-and-depth-of-resection-for-small-colorectal-polyps-hot-versus-cold-snare-polypectomy
#18
Sho Suzuki, Takuji Gotoda, Chika Kusano, Hisatomo Ikehara, Akihiro Sugita, Misa Yamauchi, Mitsuhiko Moriyama
BACKGROUND AND AIMS: Curability is associated with resection width and depth in polypectomy. We evaluated the resection width and depth achieved with hot snare polypectomy (HSP) and cold snare polypectomy (CSP) for small colorectal polyps. METHODS: In this single-center, prospective, randomized controlled study, patients with rectal or rectosigmoid polyps ≤10 mm in diameter were treated with HSP or CSP. Resection width was evaluated as mucosal defect size, measured immediately postprocedure and 1 day later...
November 6, 2017: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/29111118/hsp90-and-thioredoxin-thioredoxin-reductase-enable-the-catalytic-activity-of-clostridial-neurotoxins-inside-nerve-terminals
#19
Marco Pirazzini, Domenico Azarnia Tehran, Giulia Zanetti, Ornella Rossetto, Cesare Montecucco
Botulinum (BoNTs) and tetanus (TeNT) neurotoxins are the most toxic substances known and form the growing family of Clostridial neurotoxins (CNT), the etiologic agents of botulism and tetanus. CNT are composed of a metalloprotease light chain (L), linked via a disulfide bond to a heavy chain (H). H mediates the binding to nerve terminals and the membrane translocation of L into the cytosol, where its substrates, the three SNARE proteins, are localized. L translocation is accompanied by unfolding and, once delivered on the cytosolic side of the endosome membrane, it has to be reduced and reacquire the native fold to be active...
October 27, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29110935/successful-percutaneous-retrieval-of-a-leadless-pacemaker-due-to-an-acute-rise-in-pacing-threshold
#20
Ngai-Yin Chan, Ho-Chuen Yuen, Ngai-Shing Mok
Leadless cardiac pacemakers (LCP) have become available recently. Both its acute and long-term performance in a large population of patients remain to be tested. Subacute rise in pacing threshold has been reported as an uncommon complication. On the other hand, the retrieval technique for LCP with passive fixation mechanism has not been previously described in details. Herein we report a newly recognized complication of an acute rise in pacing threshold very soon after implantation of an LCP without radiographic dislodgement...
October 28, 2017: Indian Pacing and Electrophysiology Journal
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