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Synaptotagmin

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https://www.readbyqxmd.com/read/28432329/affinity-biosensors-using-recombinant-native-membrane-proteins-displayed-on-exosomes-application-to-botulinum-neurotoxin-b-receptor
#1
Richard Desplantes, Christian Lévêque, Benjamin Muller, Manuela Lotierzo, Géraldine Ferracci, Michel Popoff, Michael Seagar, Robert Mamoun, Oussama El Far
The development of simple molecular assays with membrane protein receptors in a native conformation still represents a challenging task. Exosomes are extracellular vesicles which, due to their stability and small size, are suited for analysis in various assay formats. Here, we describe a novel approach to sort recombinant fully native and functional membrane proteins to exosomes using a targeting peptide. Specific binding of high affinity ligands to the potassium channel Kv1.2, the G-protein coupled receptor CXCR4, and the botulinum neurotoxin type B (BoNT/B) receptor, indicated their correct assembly and outside out orientation in exosomes...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28419135/an-organotypic-slice-culture-to-study-the-formation-of-calyx-of-held-synapses-in-vitro
#2
Elin Kronander, Nicolas Michalski, Cécile Lebrand, Jean-Pierre Hornung, Ralf Schneggenburger
The calyx of Held, a large axo-somatic relay synapse containing hundreds of presynaptic active zones, is possibly the largest nerve terminal in the mammalian CNS. Studying its initial growth in-vitro might provide insights into the specification of synaptic connection size in the developing brain. However, attempts to maintain calyces of Held in organotypic cultures have not been fruitful in past studies. Here, we describe an organotypic slice culture method in which calyces of Held form in-vitro. We made coronal brainstem slices with an optimized slice angle using newborn mice in which calyces have not yet formed; the presynaptic bushy cells were genetically labeled using the Math5 promoter...
2017: PloS One
https://www.readbyqxmd.com/read/28370453/rab3a-inhibition-of-ca-2-dependent-dopamine-release-from-pc12-cells-involves-interaction-with-synaptotagmin-i
#3
Zhipan Dai, Xia Tang, Jia Chen, Xiaochao Tang, Xianchun Wang
Rab3 and synaptotagmin have been suggested to play important roles in the regulation of neurotransmitter release and, however, the molecular mechanism has not been completely clear. Here we studied the effects of Rab3A and synaptotagmin I (Syt I) on dopamine release using PC12 cells as a model system. Rab3A was demonstrated to have effects on both Ca(2+) -independent and Ca(2+) -dependent dopamine releases from the PC12 cells. Application of Rab3A (up to 2500 nM) gradually decreased the amount of Ca(2+) -dependently released dopamine, indicating that Rab3A is a negative modulator that was further supported by the increase in dopamine release caused by Rab3A knockdown...
March 29, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28363983/synaptotagmin2-syt2-drives-fast-release-redundantly-with-syt1-at-the-output-synapses-of-parvalbumin-expressing-inhibitory-neurons
#4
Brice Bouhours, Enida Gjoni, Olexiy Kochubey, Ralf Schneggenburger
Parvalbumin-expressing inhibitory neurons in the mammalian CNS are specialized for fast transmitter release at their output synapses. However, the Ca(2+) sensor(s) employed by identified inhibitory synapses, including the output synapses of PV-expressing inhibitory neurons, have only recently started to be addressed. Here, we investigated the roles of Syt1 and Syt2 at two types of fast-releasing inhibitory connections in the mammalian CNS, the MNTB to LSO glycinergic synapse, and the basket/stellate cell - Purkinje GABAergic synapse in the cerebellum...
March 31, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28363589/the-extended-synaptotagmins
#5
REVIEW
Yasunori Saheki, Pietro De Camilli
The extended-synaptotagmins (tricalbins in yeast) derive their name from their partial domain structure similarity to the synaptotagmins, which are characterized by an N-terminal membrane anchor and cytosolically exposed C2 domains. However, they differ from the synaptotagmins in localization and function. The synaptotagmins tether secretory vesicles, including synaptic vesicles, to the plasma membrane (PM) via their C2 domains and regulate their Ca(2+) triggered exocytosis. In contrast, the extended-synaptotagmins are resident proteins of the endoplasmic reticulum (ER), which tether this organelle to the plasma membrane via their C2 domains, but not as a premise to fusion of the two membranes...
March 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28355182/postsynaptic-synaptotagmins-mediate-ampa-receptor-exocytosis-during-ltp
#6
Dick Wu, Taulant Bacaj, Wade Morishita, Debanjan Goswami, Kristin L Arendt, Wei Xu, Lu Chen, Robert C Malenka, Thomas C Südhof
Strengthening of synaptic connections by NMDA (N-methyl-d-aspartate) receptor-dependent long-term potentiation (LTP) shapes neural circuits and mediates learning and memory. During the induction of NMDA-receptor-dependent LTP, Ca(2+) influx stimulates recruitment of synaptic AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors, thereby strengthening synapses. How Ca(2+) induces the recruitment of AMPA receptors remains unclear. Here we show that, in the pyramidal neurons of the hippocampal CA1 region in mice, blocking postsynaptic expression of both synaptotagmin-1 (Syt1) and synaptotagmin-7 (Syt7), but not of either alone, abolished LTP...
April 20, 2017: Nature
https://www.readbyqxmd.com/read/28348516/molecular-mechanisms-for-the-coupling-of-endocytosis-to-exocytosis-in-neurons
#7
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/28323244/itraq-based-differential-proteomic-analysis-in-mongolian-gerbil-brains-chronically-infected-with-toxoplasma-gondii
#8
Lin Lv, Yapei Wang, Weili Feng, Jorge A Hernandez, Wanyi Huang, Yuxiang Zheng, Xue Zhou, Shumei Lv, Yajun Chen, Zi-Guo Yuan
The aim of our study was to detect differentially regulated proteins and specific signaling pathways in Mongolian gerbil brains during chronic Toxoplasma gondii (T.gondii) PRU strain infection. We use a iTRAQ-based strategy to detecte 4935 proteins, out of which 110 proteins were differentially expressed (>/=2.0-fold, p value <0.05) when the brain of gerbils infected with T.gondii was compared to control brain tissues. We confirmed the authenticity and the accuracy of iTRAQ results through quantitative real-time PCR and western blot (WB), which was consistent with mass spectrometry analysis...
March 18, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28296078/botulinum-neurotoxin-type-b-uses-a-distinct-entry-pathway-mediated-by-cdc42-into-intestinal-cells-versus-neuronal-cells
#9
Chloé Connan, Marie Voillequin, Carolina Varela Chavez, Christelle Mazuet, Christian Leveque, Sandrine Vitry, Alain Vandewalle, Michel R Popoff
Botulinum neurotoxins (BoNTs) are responsible for severe flaccid paralysis by inhibiting the release of acetylcholine at the neuromuscular junctions. BoNT/B most often induces mild forms of botulism with predominant dysautonomic symptoms. In food borne botulism and botulism by intestinal colonization such as infant botulism, which are the most frequent naturally acquired forms of botulism, the digestive tract is the main entry route of BoNTs into the organism. We previously showed that BoNT/B translocates through mouse intestinal barrier by an endocytosis-dependent mechanism and subsequently targets neuronal cells, mainly cholinergic neurons, in the intestinal mucosa and musculosa...
March 11, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28292915/a-cascade-of-multiple-proteins-and-lipids-catalyzes-membrane-fusion
#10
William Wickner, Josep Rizo
Recent studies suggest revisions to the SNARE paradigm of membrane fusion. Membrane tethers and/or SNAREs recruit proteins of the Sec 1/Munc18 family to catalyze SNARE assembly into trans-complexes. SNARE-domain zippering draws the bilayers into immediate apposition and provides a platform to position fusion triggers such as Sec 17/α-SNAP and/or synaptotagmin, which insert their apolar "wedge" domains into the bilayers, initiating the lipid rearrangements of fusion.
March 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28280457/the-structure-of-the-synaptic-vesicle-plasma-membrane-interface-constrains-snare-models-of-rapid-synchronous-exocytosis-at-nerve-terminals
#11
REVIEW
Cameron B Gundersen
Contemporary models of neurotransmitter release invoke direct or indirect interactions between the Ca(2+) sensor, synaptotagmin and the incompletely zippered soluble, N-ethyl-maleimide-sensitive factor attachment protein receptor (SNARE) complex. However, recent electron microscopic (EM) investigations have raised pragmatic issues concerning the mechanism by which SNAREs trigger membrane fusion at nerve terminals. The first issue is related to the finding that the area of contact between a "fully primed" synaptic vesicle and the plasma membrane can exceed 600 nm(2)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28265280/interface-symbiotic-membrane-formation-in-root-nodules-of-medicago-truncatula-the-role-of-synaptotagmins-mtsyt1-mtsyt2-and-mtsyt3
#12
Aleksandr Gavrin, Olga Kulikova, Ton Bisseling, Elena E Fedorova
Symbiotic bacteria (rhizobia) are maintained and conditioned to fix atmospheric nitrogen in infected cells of legume root nodules. Rhizobia are confined to the asymmetrical protrusions of plasma membrane (PM): infection threads (IT), cell wall-free unwalled droplets and symbiosomes. These compartments rapidly increase in surface and volume due to the microsymbiont expansion, and remarkably, the membrane resources of the host cells are targeted to interface membrane quite precisely. We hypothesized that the change in the membrane tension around the expanding microsymbionts creates a vector for membrane traffic toward the symbiotic interface...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28254618/parkin-promotes-proteasomal-degradation-of-synaptotagmin-iv-by-accelerating-polyubiquitination
#13
Hiroyuki Kabayama, Naoko Tokushige, Makoto Takeuchi, Miyuki Kabayama, Mitsunori Fukuda, Katsuhiko Mikoshiba
Parkin is an E3 ubiquitin ligase whose mutations cause autosomal recessive juvenile Parkinson's disease (PD). Unlike the human phenotype, parkin knockout (KO) mice show no apparent dopamine neuron degeneration, although they demonstrate reduced expression and activity of striatal mitochondrial proteins believed to be necessary for neuronal survival. Instead, parkin-KO mice show reduced striatal evoked dopamine release, abnormal synaptic plasticity, and non-motor symptoms, all of which appear to mimic the preclinical features of Parkinson's disease...
February 22, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28238652/the-er-stress-sensor-perk-coordinates-er-plasma-membrane-contact-site-formation-through-interaction-with-filamin-a-and-f-actin-remodeling
#14
Alexander R van Vliet, Francesca Giordano, Sarah Gerlo, Inmaculada Segura, Sofie Van Eygen, Geert Molenberghs, Susana Rocha, Audrey Houcine, Rita Derua, Tom Verfaillie, Jeroen Vangindertael, Herlinde De Keersmaecker, Etienne Waelkens, Jan Tavernier, Johan Hofkens, Wim Annaert, Peter Carmeliet, Afshin Samali, Hideaki Mizuno, Patrizia Agostinis
Loss of ER Ca(2+) homeostasis triggers endoplasmic reticulum (ER) stress and drives ER-PM contact sites formation in order to refill ER-luminal Ca(2+). Recent studies suggest that the ER stress sensor and mediator of the unfolded protein response (UPR) PERK regulates intracellular Ca(2+) fluxes, but the mechanisms remain elusive. Here, using proximity-dependent biotin identification (BioID), we identified the actin-binding protein Filamin A (FLNA) as a key PERK interactor. Cells lacking PERK accumulate F-actin at the cell edges and display reduced ER-PM contacts...
March 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28209913/rapid-imaging-of-tumor-cell-death-in-vivo-using-the-c2a-domain-of-synaptotagmin-i
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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