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Synaptotagmin

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https://www.readbyqxmd.com/read/28209913/rapid-imaging-of-tumor-cell-death-in-vivo-using-the-c2a-domain-of-synaptotagmin-i
#1
André A Neves, Bangwen Xie, Sarah Fawcett, Israt S Alam, Timothy H Witney, Maaike M de Backer, Julia Summers, William Hughes, Sarah McGuire, Dmitry Soloviev, Jodie Miller, William J Howat, De-En Hu, Tiago B Rodrigues, David Y Lewis, Kevin M Brindle
Cell death is an important target for imaging the early response of tumors to treatment. We describe here validation of a phosphatidylserine-binding agent for detecting tumor cell death in vivo based on the C2A domain of Synaptotagmin-I. Methods: The capability of near infrared fluorophore-labeled and 99mTechnetium- and (111)Indium-labeled derivatives of C2Am for imaging tumor cell death, using planar near infrared fluorescence (NIRF) imaging and single photon computed tomography (SPECT) respectively, was evaluated in implanted and genetically engineered mouse models of lymphoma and in a human colorectal xenograft...
February 16, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28194317/pull-down-combined-with-proteomic-strategy-reveals-functional-diversity-of-synaptotagmin-i
#2
Tianyao Guo, Zhigui Duan, Jia Chen, Chunliang Xie, Ying Wang, Ping Chen, Xianchun Wang
Synaptotagmin I (Syt I) is most abundant in the brain and is involved in multiple cellular processes. Its two C2 domains, C2A and C2B, are the main functional regions. Our present study employed a pull-down combined with proteomic strategy to identify the C2 domain-interacting proteins to comprehensively understand the biological roles of the C2 domains and thus the functional diversity of Syt I. A total of 135 non-redundant proteins interacting with the C2 domains of Syt I were identified. Out of them, 32 and 64 proteins only bound to C2A or C2B domains, respectively, and 39 proteins bound to both of them...
2017: PeerJ
https://www.readbyqxmd.com/read/28193235/dynamic-presenilin-1-and-synaptotagmin-1-interaction-modulates-exocytosis-and-amyloid-%C3%AE-production
#3
Katarzyna Marta Zoltowska, Masato Maesako, Iryna Lushnikova, Shuko Takeda, Laura J Keller, Galina Skibo, Bradley T Hyman, Oksana Berezovska
BACKGROUND: Alzheimer's disease (AD)-linked protein, presenilin 1 (PS1), is present at the synapse, and the knock-out of presenilin in mice leads to synaptic dysfunction. On the other hand, synaptic activity was shown to influence PS1-dependent generation of distinct amyloid β (Aβ) species. However, the precise nature of these regulations remains unclear. The current study reveals novel role of PS1 at the synapse, and deciphers how PS1 and synaptic vesicle-associated protein, synaptotagmin 1 (Syt1) modulate each other functions in neurons via direct activity-triggered interaction...
February 13, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28191915/routes-and-mechanisms-of-post-endosomal-cholesterol-trafficking-a-story-that-never-ends
#4
REVIEW
Jie Luo, Luyi Jiang, Hongyuan Yang, Bao-Liang Song
Mammalian cells acquire most exogenous cholesterol through receptor-mediated endocytosis of low-density lipoproteins (LDLs). After internalization, LDL cholesteryl esters are hydrolyzed to release free cholesterol, which then translocates to late endosomes (LEs)/lysosomes (LYs) and incorporates into the membranes by coordinated actions of Niemann-Pick type C (NPC) 1 and NPC2 proteins. However, how cholesterol exits LEs/LYs and moves to other organelles remain largely unclear. Growing evidence has suggested that nonvesicular transport is critically involved in the post-endosomal cholesterol trafficking...
February 13, 2017: Traffic
https://www.readbyqxmd.com/read/28173138/synaptotagmin-2-and-1-linked-to-neurotransmission-impairment-and-vulnerability-in-spinal-muscular-atrophy
#5
Rocío Tejero, Mario Lopez-Manzaneda, Saravanan Arumugam, Lucía Tabares
No abstract text is available yet for this article.
November 1, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28130000/replicated-association-of-synaptotagmin-syt1-with-adhd-and-its-broader-influence-in-externalizing-behaviors
#6
Renata Basso Cupertino, Jaqueline Bohrer Schuch, Cibele Edom Bandeira, Bruna Santos da Silva, Diego Luiz Rovaris, Djenifer B Kappel, Verônica Contini, Angélica Salatino-Oliveira, Eduardo Schneider Vitola, Rafael Gomes Karam, Mara Helena Hutz, Luis Augusto Rohde, Eugenio Horacio Grevet, Claiton Henrique Dotto Bau, Nina Roth Mota
Attention-Deficit/Hyperactivity Disorder (ADHD) is a common psychiatric disorder, affecting both children and adults. The Soluble N-ethylmaleimide sensitive factor Attachment REceptors (SNARE) complex has been implicated in ADHD pathophysiology since it is a key component of neurotransmitter release events and neurodevelopment processes, and SNPs in this complex have been associated with ADHD. Here we aim to analyze the effects of SNARE complex variants on ADHD susceptibility and its clinical heterogeneity in affected adults...
January 24, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28116546/cortical-synaptic-transmission-and-plasticity-in-acute-liver-failure-are-decreased-by-presynaptic-events
#7
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
https://www.readbyqxmd.com/read/28111077/synaptotagmin-1-and-synaptotagmin-7-dependent-fusion-mechanisms-target-synaptic-vesicles-to-kinetically-distinct-endocytic-pathways
#8
Ying C Li, Natali L Chanaday, Wei Xu, Ege T Kavalali
Synaptic vesicle recycling is essential for maintaining normal synaptic function. The coupling of exocytosis and endocytosis is assumed to be Ca(2+) dependent, but the exact role of Ca(2+) and its key effector synaptotagmin-1 (syt1) in regulation of endocytosis is poorly understood. Here, we probed the role of syt1 in single- as well as multi-vesicle endocytic events using high-resolution optical recordings. Our experiments showed that the slowed endocytosis phenotype previously reported after syt1 loss of function can also be triggered by other manipulations that promote asynchronous release such as Sr(2+) substitution and complexin loss of function...
February 8, 2017: Neuron
https://www.readbyqxmd.com/read/28099850/synaptotagmin-2-is-the-fast-ca-2-sensor-at-a-central-inhibitory-synapse
#9
Chong Chen, Itaru Arai, Rachel Satterfield, Samuel M Young, Peter Jonas
GABAergic synapses in brain circuits generate inhibitory output signals with submillisecond latency and temporal precision. Whether the molecular identity of the release sensor contributes to these signaling properties remains unclear. Here, we examined the Ca(2+) sensor of exocytosis at GABAergic basket cell (BC) to Purkinje cell (PC) synapses in cerebellum. Immunolabeling suggested that BC terminals selectively expressed synaptotagmin 2 (Syt2), whereas synaptotagmin 1 (Syt1) was enriched in excitatory terminals...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28057568/localization-of-rab3a-binding-site-on-c2a-domain-of-synaptotagmin-i-to-reveal-its-regulatory-mechanism
#10
Xia Tang, Chunliang Xie, Ying Wang, Xianchun Wang
Synaptotagmin I (Syt I) functions in the regulation of neurotransmitter release and multiple other cellular processes through its C2 domain binding to other molecules. Our previous study demonstrated that Rab3A, a small GTP-binding protein, is a new interacting partner of Syt I and could bind to both of the C2 domains; the polylysine motif in C2B is a key site for Rab3A binding, but the binding site on C2A is not clear. In order to localize Rab3-binding site on C2A and reveal the relevant regulatory mechanism, in the present study we investigated the interaction between recombinant Rab3A and various C2A mutants...
January 3, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28026832/significance-of-syt8-for-the-detection-prediction-and-treatment-of-peritoneal-metastasis-from-gastric-cancer
#11
Mitsuro Kanda, Dai Shimizu, Haruyoshi Tanaka, Chie Tanaka, Daisuke Kobayashi, Masamichi Hayashi, Naoki Iwata, Yukiko Niwa, Suguru Yamada, Tsutomu Fujii, Hiroyuki Sugimoto, Kenta Murotani, Michitaka Fujiwara, Yasuhiro Kodera
OBJECTIVE: To develop novel diagnostic and therapeutic targets specific for peritoneal metastasis of gastric cancer (GC). BACKGROUND: Advanced GC frequently recurs because of undetected micrometastases even after curative resection. Peritoneal metastasis has been the most frequent recurrent pattern after gastrectomy and is incurable. METHODS: We conducted a recurrence pattern-specific transcriptome analysis in an independent cohort of 16 patients with stage III GC who underwent curative gastrectomy and adjuvant S-1 for screening candidate molecules specific for peritoneal metastasis of GC...
December 6, 2016: Annals of Surgery
https://www.readbyqxmd.com/read/27997124/differential-membrane-binding-mechanics-of-synaptotagmin-isoforms-observed-in-atomic-detail
#12
Josh V Vermaas, Emad Tajkhorshid
Synaptotagmin (Syt) is a membrane-associated protein involved in vesicle fusion through the SNARE complex that is found throughout the human body in 17 different isoforms. These isoforms have two membrane-binding C2 domains, which sense Ca(2+) and thereby promote anionic membrane binding and lead to vesicle fusion. Through molecular dynamics simulations using the highly mobile membrane mimetic acclerated bilayer model, we have investigated how small protein sequence changes in the Ca(2+)-binding loops of the C2 domains may give rise to the experimentally determined difference in binding kinetics between Syt-1 and Syt-7 isoforms...
December 20, 2016: Biochemistry
https://www.readbyqxmd.com/read/27988858/sequence-specific-assignment-of-methyl-groups-from-the-neuronal-snare-complex-using-lanthanide-induced-pseudocontact-shifts
#13
Yun-Zu Pan, Bradley Quade, Kyle D Brewer, Monika Szabo, James D Swarbrick, Bim Graham, Josep Rizo
Neurotransmitter release depends critically on the neuronal SNARE complex formed by syntaxin-1, SNAP-25 and synaptobrevin, as well as on other proteins such as Munc18-1, Munc13-1 and synaptotagmin-1. Although three-dimensional structures are available for these components, it is still unclear how they are assembled between the synaptic vesicle and plasma membranes to trigger fast, Ca(2+)-dependent membrane fusion. Methyl TROSY NMR experiments provide a powerful tool to study complexes between these proteins, but assignment of the methyl groups of the SNARE complex is hindered by its limited solubility...
December 2016: Journal of Biomolecular NMR
https://www.readbyqxmd.com/read/27984133/perinatal-exposure-to-lead-pb-induces-ultrastructural-and-molecular-alterations-in-synapses-of-rat-offspring
#14
Magdalena Gąssowska, Irena Baranowska-Bosiacka, Joanna Moczydłowska, Małgorzata Frontczak-Baniewicz, Magdalena Gewartowska, Lidia Strużyńska, Izabela Gutowska, Dariusz Chlubek, Agata Adamczyk
Lead (Pb), environmentally abundant heavy-metal pollutant, is a strong toxicant for the developing central nervous system. Pb intoxication in children, even at low doses, is found to affect learning and memorizing, with devastating effects on cognitive function and intellectual development. However, the precise mechanism by which Pb impairs synaptic plasticity is not fully elucidated. The purpose of this study was to investigate the effect of pre- and neonatal exposure to low dose of Pb (with Pb concentrations in whole blood below 10μg/dL) on the synaptic structure and the pre- and postsynaptic proteins expression in the developing rat brain...
October 29, 2016: Toxicology
https://www.readbyqxmd.com/read/27974903/morphine-antidependence-of-erythroxylum-cuneatum-miq-kurz-in-neurotransmission-processes-in-vitro
#15
Noor Azuin Suliman, Mohamad Aris Mohd Moklas, Che Norma Mat Taib, Mohd Ilham Adenan, Mohamad Taufik Hidayat Baharuldin, Rusliza Basir, Zulkhairi Amom
Opiate abuse has been studied to cause adaptive changes observed in the presynaptic release and the mediated-synaptic plasticity proteins. The involvement of neuronal SNARE proteins reveals the role of the neurotransmitter release in expressing the opioid actions. The present study was designed to determine the effect of the alkaloid extract of Erythroxylum cuneatum (E. cuneatum) against chronic morphine and the influences of E. cuneatum on neurotransmission processes observed in vitro. The human neuroblastoma cell line, SK-N-SH, was treated with the morphine, methadone, or E...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/27974193/perinatal-exposure-to-lead-pb-induces-ultrastructural-and-molecular-alterations-in-synapses-of-rat-offspring
#16
Magdalena Gąssowska, Irena Baranowska-Bosiacka, Joanna Moczydłowska, Małgorzata Frontczak-Baniewicz, Magdalena Gewartowska, Lidia Strużyńska, Izabela Gutowska, Dariusz Chlubek, Agata Adamczyk
Lead (Pb), environmentally abundant heavy-metal pollutant, is a strong toxicant for the developing central nervous system. Pb intoxication in children, even at low doses, is found to affect learning and memorizing, with devastating effects on cognitive function and intellectual development. However, the precise mechanism by which Pb impairs synaptic plasticity is not fully elucidated. The purpose of this study was to investigate the effect of pre- and neonatal exposure to low dose of Pb (with Pb concentrations in whole blood below 10μg/dL) on the synaptic structure and the pre- and postsynaptic proteins expression in the developing rat brain...
December 12, 2016: Toxicology
https://www.readbyqxmd.com/read/27921176/two-feet-on-the-membrane-uptake-of-clostridial-neurotoxins
#17
Andreas Rummel
The extraordinary potency of botulinum neurotoxins (BoNT) and tetanus neurotoxin (TeNT) is mediated by their high neurospecificity, targeting peripheral cholinergic motoneurons leading to flaccid and spastic paralysis, respectively, and successive respiratory failure. Complex polysialo gangliosides accumulate BoNT and TeNT on the plasma membrane. The ganglioside binding in BoNT/A, B, E, F, G, and TeNT occurs via a conserved ganglioside-binding pocket within the most carboxyl-terminal 25 kDa domain HCC, whereas BoNT/C, DC, and D display here two different ganglioside binding sites...
December 1, 2016: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/27881774/interactions-between-snap-25-and-synaptotagmin-1-are-involved-in-vesicle-priming-clamping-spontaneous-and-stimulating-evoked-neurotransmission
#18
Melanie Schupp, Jörg Malsam, Marvin Ruiter, Andrea Scheutzow, Keimpe D B Wierda, Thomas H Söllner, Jakob B Sørensen
: Whether interactions between synaptotagmin-1 (syt-1) and the soluble NSF attachment protein receptors (SNAREs) are required during neurotransmission is debated. We examined five SNAP-25 mutations designed to interfere with syt-1 interactions. One mutation, D51/E52/E55A, targeted negative charges within region II of the primary interface (Zhou et al., 2015); two mutations targeted region I (D166A and D166/E170A) and one mutation targeted both (D51/E52/E55/D166A). The final mutation (D186/D193A) targeted C-terminal residues not expected to interact with syt-1...
November 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27811083/arabidopsis-syt1-maintains-stability-of-cortical-endoplasmic-reticulum-networks-and-vap27-1-enriched-endoplasmic-reticulum-plasma-membrane-contact-sites
#19
Wei Siao, Pengwei Wang, Boris Voigt, Patrick J Hussey, Frantisek Baluska
Arabidopsis synaptotagmin 1 (SYT1) is localized on the endoplasmic reticulum-plasma membrane (ER-PM) contact sites in leaf and root cells. The ER-PM localization of Arabidopsis SYT1 resembles that of the extended synaptotagmins (E-SYTs) in animal cells. In mammals, E-SYTs have been shown to regulate calcium signaling, lipid transfer, and endocytosis. Arabidopsis SYT1 was reported to be essential for maintaining cell integrity and virus movement. This study provides detailed insight into the subcellular localization of SYT1 and VAP27-1, another ER-PM-tethering protein...
November 2016: Journal of Experimental Botany
https://www.readbyqxmd.com/read/27794539/human-r1441c-lrrk2-regulates-the-synaptic-vesicle-proteome-and-phosphoproteome-in-a-drosophila-model-of-parkinson-s-disease
#20
Md Shariful Islam, Hendrik Nolte, Wright Jacob, Anna B Ziegler, Stefanie Pütz, Yael Grosjean, Karolina Szczepanowska, Aleksandra Trifunovic, Thomas Braun, Hermann Heumann, Rolf Heumann, Bernhard Hovemann, Darren J Moore, Marcus Krüger
Mutations in leucine-rich repeat kinase 2 (LRRK2) cause late-onset, autosomal dominant familial Parkinson's disease (PD) and variation at the LRRK2 locus contributes to the risk for idiopathic PD. LRRK2 can function as a protein kinase and mutations lead to increased kinase activity. To elucidate the pathophysiological mechanism of the R1441C mutation in the GTPase domain of LRRK2, we expressed human wild-type or R1441C LRRK2 in dopaminergic neurons of Drosophila and observe reduced locomotor activity, impaired survival and an age-dependent degeneration of dopaminergic neurons thereby creating a new PD-like model...
October 29, 2016: Human Molecular Genetics
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