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Synaptotagmin

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https://www.readbyqxmd.com/read/28600435/rassf4-controls-soce-and-er-pm-junctions-through-regulation-of-pi-4-5-p2
#1
Yu-Ju Chen, Chi-Lun Chang, Wan-Ru Lee, Jen Liou
RAS association domain family 4 (RASSF4) is involved in tumorigenesis and regulation of the Hippo pathway. In this study, we identify new functional roles of RASSF4. First, we discovered that RASSF4 regulates store-operated Ca(2+) entry (SOCE), a fundamental Ca(2+) signaling mechanism, by affecting the translocation of the endoplasmic reticulum (ER) Ca(2+) sensor stromal interaction molecule 1 (STIM1) to ER-plasma membrane (PM) junctions. It was further revealed that RASSF4 regulates the formation of ER-PM junctions and the ER-PM tethering function of extended synaptotagmins E-Syt2 and E-Syt3...
June 9, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28574251/non-native-metal-ion-reveals-the-role-of-electrostatics-in-synaptotagmin-1-membrane-interactions
#2
Sachin Katti, Sarah B Nyenhuis, Bin Her, Atul K Srivastava, Alexander B Taylor, P John Hart, David S Cafiso, Tatyana I Igumenova
C2 domains are independently folded modules that often target their host proteins to anionic membranes in a Ca(2+)-dependent manner. In these cases, membrane association is triggered by Ca(2+) binding to the negatively charged loop region of the C2 domain. Here, we used a non-native metal ion, Cd(2+), in lieu of Ca(2+) to gain insight into the contributions made by long-range Coulombic interactions and direct metal ion-lipid bridging to membrane binding. Using X-ray crystallography, NMR, Förster resonance energy transfer, and vesicle cosedimentation assays, we demonstrate that, although Cd(2+) binds to the loop region of C2A/B domains of synaptotagmin 1 with high affinity, long-range Coulombic interactions are too weak to support membrane binding of individual domains...
June 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/28554774/tubular-lipid-binding-proteins-tulips-growing-everywhere
#3
REVIEW
Louise H Wong, Tim P Levine
Tubular lipid binding proteins (TULIPs) have become a focus of interest in the cell biology of lipid signalling, lipid traffic and membrane contact sites. Each tubular domain has an internal pocket with a hydrophobic lining that can bind a hydrophobic molecule such as a lipid. This allows TULIP proteins to carry lipids through the aqueous phase. TULIP domains were first found in a large family of extracellular proteins related to the bacterial permeability-inducing protein (BPI) and cholesterol ester transfer protein (CETP)...
May 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28550152/er-plasma-membrane-contact-sites-contribute-to-autophagosome-biogenesis-by-regulation-of-local-pi3p-synthesis
#4
Anna Chiara Nascimbeni, Francesca Giordano, Nicolas Dupont, Daniel Grasso, Maria I Vaccaro, Patrice Codogno, Etienne Morel
The double-membrane-bound autophagosome is formed by the closure of a structure called the phagophore, origin of which is still unclear. The endoplasmic reticulum (ER) is clearly implicated in autophagosome biogenesis due to the presence of the omegasome subdomain positive for DFCP1, a phosphatidyl-inositol-3-phosphate (PI3P) binding protein. Contribution of other membrane sources, like the plasma membrane (PM), is still difficult to integrate in a global picture. Here we show that ER-plasma membrane contact sites are mobilized for autophagosome biogenesis, by direct implication of the tethering extended synaptotagmins (E-Syts) proteins...
May 26, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28534241/a-genetic-variant-in-fign-gene-reduces-the-risk-of-congenital-heart-disease-in-han-chinese-populations
#5
Dan Wang, Maoping Chu, Feng Wang, Aihua Zhou, Miaohua Ruan, Yiming Chen
Congenital heart disease (CHD) is one of the most common birth anomalies worldwide. Folate deficiency is an independent risk factor for CHD. Genome-wide association studies (GWAS) revealed that human folate level could be significantly influenced by fidgetin (FIGN), methylenetetrahydrofolate reductase (MTHFR), prickle homolog 2 (PRICKLE2), synaptotagmin 9 (SYT9), gamma-aminobutyric acid B receptor 2 (GABBR2), and alkaline phosphatase (ALPL) genes. The association between the above-mentioned six variants and CHD was examined in the two independent case-control studies in a total of 868 CHD patients and 931 healthy controls...
May 22, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28521135/synaptotagmin-7-mediated-asynchronous-release-boosts-high-fidelity-synchronous-transmission-at-a-central-synapse
#6
Fujun Luo, Thomas C Südhof
Synchronous release triggered by Ca(2+) binding to synaptotagmin-1, -2, or -9 is thought to drive fast synaptic transmission, whereas asynchronous release induced by Ca(2+) binding to synaptotagmin-7 is thought to produce delayed synaptic signaling, enabling prolonged synaptic computations. However, it is unknown whether synaptotagmin-7-dependent asynchronous release performs a physiological function at fast synapses lacking a prolonged signaling mode, such as the calyx of Held synapse. Here, we show at the calyx synapse that synaptotagmin-7-dependent asynchronous release indeed does not produce a prolonged synaptic signal after a stimulus train and does not contribute to short-term plasticity, but induces a steady-state, asynchronous postsynaptic current during stimulus trains...
May 17, 2017: Neuron
https://www.readbyqxmd.com/read/28521120/synaptotagmins-that-s-why-so-many
#7
Chong Chen, Peter Jonas
Synaptotagmin 7 (Syt7) was originally identified as a slow Ca(2+) sensor for lysosome fusion, but its function at fast synapses is controversial. The paper by Luo and Südhof (2017) in this issue of Neuron shows that at the calyx of Held in the auditory brainstem Syt7 triggers asynchronous release during stimulus trains, resulting in reliable and temporally precise high-frequency transmission. Thus, a slow Ca(2+) sensor contributes to the fast signaling properties of the calyx synapse.
May 17, 2017: Neuron
https://www.readbyqxmd.com/read/28515322/g%C3%AE-%C3%AE-directly-modulates-vesicle-fusion-by-competing-with-synaptotagmin-for-binding-to-neuronal-snare-proteins-embedded-in-membranes
#8
Zack Zurawski, Brian Page, Michael C Chicka, Rebecca L Brindley, Christopher A Wells, Anita M Preininger, Karren Hyde, James A Gilbert, Osvaldo Cruz-Rodriguez, Kevin P M Currie, Edwin R Chapman, Simon Alford, Heidi E Hamm
Gi/o-coupled GPCRs can inhibit neurotransmitter release at synapses via multiple mechanisms. In addition to Gβγ-mediated modulation of voltage-gated calcium channels(VGCC), inhibition can also be mediated through the direct interaction of Gβγ subunits with the soluble N-ethylmaleimide attachment protein receptor (SNARE) complex of the vesicle fusion apparatus. Binding studies with soluble SNARE complexes have shown that Gβγ binds to both ternary SNARE complexes, t-SNARE heterodimers, and monomeric SNAREs, competing with synaptotagmin(syt)1 for binding sites on t-SNARE...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28484240/paternal-spatial-training-enhances-offspring-s-cognitive-performance-and-synaptic-plasticity-in-wild-type-but-not-improve-memory-deficit-in-alzheimer-s-mice
#9
Shujuan Zhang, Xiaoguang Li, Zhouyi Wang, Yanchao Liu, Yuan Gao, Lu Tan, Enjie Liu, Qiuzhi Zhou, Cheng Xu, Xin Wang, Gongping Liu, Haote Chen, Jian-Zhi Wang
Recent studies suggest that spatial training can maintain associative memory capacity in Tg2576 mice, but it is not known whether the beneficial effects can be inherited from the trained fathers to their offspring. Here, we exposed male wild-type and male 3XTg Alzheimer disease (AD) mice (3-m old) respectively to spatial training for one week and assessed the transgenerational effects in the F1 offspring when they were grown to 7-m old. We found that the paternal spatial training significantly enhanced progeny's spatial cognitive performance and synaptic transmission in wild-type mice...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28461697/exocytosis-related-genes-and-response-to-methylphenidate-treatment-in-adults-with-adhd
#10
B S da Silva, R B Cupertino, D L Rovaris, J B Schuch, D B Kappel, D Müller, C E Bandeira, M M Victor, R G Karam, N R Mota, L A Rohde, V Contini, E H Grevet, C H D Bau
Experimental studies have demonstrated that methylphenidate (MPH) modulates the synaptic vesicle trafficking and synaptotagmin-1 (SytI) mRNA levels. SytI is a regulatory protein of the SNARE complex, a neurotransmitter exocytosis mediator. Despite this evidence, most SNARE complex-related genes have never been evaluated in attention-deficit/hyperactivity disorder (ADHD) pharmacogenetics. This study evaluates, for we believe the first time, polymorphisms on the SNARE complex-related genes STX1A (rs2228607), VAMP2 (26bp Ins/Del) and SYT1 (rs1880867 and rs2251214) on the response to immediate-release methylphenidate (IR-MPH) in a naturalistic sample of adults with ADHD...
May 2, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28456331/complexin-binding-to-membranes-and-acceptor-t-snares-explains-its-clamping-effect-on-fusion
#11
Rafal Zdanowicz, Alex Kreutzberger, Binyong Liang, Volker Kiessling, Lukas K Tamm, David S Cafiso
Complexin-1 is a SNARE effector protein that decreases spontaneous neurotransmitter release and enhances evoked release. Complexin binds to the fully assembled four-helical neuronal SNARE core complex as revealed in competing molecular models derived from x-ray crystallography. Presently, it is unclear how complexin binding to the postfusion complex accounts for its effects upon spontaneous and evoked release in vivo. Using a combination of spectroscopic and imaging methods, we characterize in molecular detail how complexin binds to the 1:1 plasma membrane t-SNARE complex of syntaxin-1a and SNAP-25 while simultaneously binding the lipid bilayer at both its N- and C-terminal ends...
April 26, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28432329/affinity-biosensors-using-recombinant-native-membrane-proteins-displayed-on-exosomes-application-to-botulinum-neurotoxin-b-receptor
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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 type B (BoNT/B) most often induces mild forms of botulism with predominant dysautonomic symptoms. In food borne botulism and botulism by intestinal colonisation 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
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