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Synaptotagmin

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https://www.readbyqxmd.com/read/27881774/interactions-between-snap-25-and-synaptotagmin-1-are-involved-in-vesicle-priming-clamping-spontaneous-and-stimulating-evoked-neurotransmission
#1
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
#2
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
#3
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
https://www.readbyqxmd.com/read/27793683/structural-analysis-of-ca-2-binding-pocket-of-synaptotagmin-5-c2a-domain
#4
Xiaoting Qiu, Junyi Ge, Yongxiang Gao, Maikun Teng, Liwen Niu
Synaptotagmins constitute a family of multifunctional integral membrane proteins found predominantly on vesicles in neural and endocrine tissues. 17 isoforms of synaptotagmin family in mammals have been identified, 7 isoforms among them are known to be able to bind Ca(2+) via their C2 domains. This study presents the crystal structure of the first C2 domain (C2A domain) of synaptotagmin 5 complexed with Ca(2+) at 1.90Å resolution. Comparison of the Ca(2+)-binding pocket of synaptotagmin 5 C2A domain with other synaptotagmin C2 domains demonstrated that a serine residue locating at Ca(2+)-binding loop probably responsible to the conformational variation of Ca(2+)-binding pocket, and thus impacts the Ca(2+)-binding mechanism of C2 domain, which is verified by structural analysis of the serine mutant and Ca(2+)-binding assays via isothermal titration calorimetry...
October 25, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27791979/ptdinsp2-and-ptdser-cooperate-to-trap-synaptotagmin-1-to-the-plasma-membrane-in-the-presence-of-calcium
#5
Ángel Pérez-Lara, Anusa Thapa, Sarah B Nyenhuis, David A Nyenhuis, Partho Halder, Michael Tietzel, Kai Tittmann, David S Cafiso, Reinhard Jahn
The Ca(2+)-sensor synaptotagmin-1 that triggers neuronal exocytosis binds to negatively charged membrane lipids (mainly phosphatidylserine (PtdSer) and phosphoinositides (PtdIns)) but the molecular details of this process are not fully understood. Using quantitative thermodynamic, kinetic and structural methods, we show that synaptotagmin-1 (from Rattus norvegicus and expressed in Escherichia coli) binds to PtdIns(4,5)P2 via a polybasic lysine patch in the C2B domain, which may promote the priming or docking of synaptic vesicles...
October 28, 2016: ELife
https://www.readbyqxmd.com/read/27771350/synaptotagmin-7-and-syncrip-proteins-are-ubiquitously-expressed-in-the-rat-brain-and-co-localize-in-purkinje-neurons
#6
Larisa Tratnjek, Marko Živin, Gordana Glavan
Synaptotagmin 7 (SYT7) is ubiquitously expressed calcium sensor, involved in neuronal membrane trafficking. Immunoprecipitation experiments demonstrated that SYT7 interacts with Synaptotagmin-binding, cytoplasmic RNA-interacting protein (SYNCRIP). SYNCRIP is a component of mRNA granules, which are transported to dendrites and are prerequisite for synaptic plasticity. Given the potential significance of SYT7 regulation in processes of neurodegeneration, which are characterized by high level of synaptic vulnerability, we aimed to analyse and compare the distribution of SYT7 and SYNCRIP proteins in the adult rat striatum, hippocampus, cerebral and cerebellar cortex...
October 19, 2016: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/27732855/the-rna-binding-protein-syncrip-is-a-component-of-the-hepatocyte-exosomal-machinery-controlling-microrna-sorting
#7
Laura Santangelo, Giorgio Giurato, Carla Cicchini, Claudia Montaldo, Carmine Mancone, Roberta Tarallo, Cecilia Battistelli, Tonino Alonzi, Alessandro Weisz, Marco Tripodi
Despite clear evidence that exosomal microRNAs (miRNAs) are able to modulate the cellular microenvironment and that exosomal RNA cargo selection is deregulated in pathological conditions, the mechanisms controlling specific RNA sorting into extracellular vesicles are still poorly understood. Here, we identified the RNA binding protein SYNCRIP (synaptotagmin-binding cytoplasmic RNA-interacting protein; also known as hnRNP-Q or NSAP1) as a component of the hepatocyte exosomal miRNA sorting machinery. SYNCRIP knockdown impairs sorting of miRNAs in exosomes...
October 11, 2016: Cell Reports
https://www.readbyqxmd.com/read/27731902/c2-domain-containing-calcium-sensors-in-neuroendocrine-secretion
#8
REVIEW
Paulo S Pinheiro, Sébastien Houy, Jakob B Sørensen
The molecular mechanisms for calcium-triggered membrane fusion have long been sought for, and detailed models now exist that account for at least some of the functions of the many proteins involved in the process. Key players in the fusion reaction are a group of proteins that, upon binding to calcium, trigger the merger of cargo-filled vesicles with the plasma membrane. Low-affinity, fast-kinetics calcium sensors of the synaptotagmin family - especially synaptotagmin-1 and synaptotagmin-2 - are the main calcium sensors for fast exocytosis triggering in many cell types...
October 12, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27731796/advances-in-x-ray-free-electron-laser-xfel-diffraction-data-processing-applied-to-the-crystal-structure-of-the-synaptotagmin-1-snare-complex
#9
Artem Y Lyubimov, Monarin Uervirojnangkoorn, Oliver B Zeldin, Qiangjun Zhou, Minglei Zhao, Aaron S Brewster, Tara Michels-Clark, James M Holton, Nicholas K Sauter, William I Weis, Axel T Brunger
X-ray free electron lasers (XFELs) reduce the effects of radiation damage on macromolecular diffraction data and thereby extend the limiting resolution. Previously, we adapted classical post-refinement techniques to XFEL diffraction data to produce accurate diffraction data sets from a limited number of diffraction images (Uervirojnangkoorn et al., 2015), and went on to use these techniques to obtain a complete data set from crystals of the synaptotagmin-1 / SNARE complex and to determine the structure at 3...
October 12, 2016: ELife
https://www.readbyqxmd.com/read/27723113/synaptic-vesicle-pool-specific-modification-of-neurotransmitter-release-by-intravesicular-free-radical-generation
#10
Olusoji A T Afuwape, Catherine R Wasser, Thomas Schikorski, Ege T Kavalali
KEY POINTS: Synaptic transmission is mediated by the release of neurotransmitters from synaptic vesicles in response to stimulation or through the spontaneous fusion of a synaptic vesicle with the presynaptic plasma membrane. There is growing evidence that synaptic vesicles undergoing spontaneous fusion versus those fusing in response to stimuli are functionally distinct. In this study, we acutely probe the effects of intravesicular free radical generation on synaptic vesicles that fuse spontaneously or in response to stimuli...
October 10, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27716408/the-pre-synaptic-vesicle-protein-synaptotagmin-is-a-novel-biomarker-for-alzheimer-s-disease
#11
Annika Öhrfelt, Ann Brinkmalm, Julien Dumurgier, Gunnar Brinkmalm, Oskar Hansson, Henrik Zetterberg, Elodie Bouaziz-Amar, Jacques Hugon, Claire Paquet, Kaj Blennow
BACKGROUND: Synaptic degeneration is a central pathogenic event in Alzheimer's disease that occurs early during the course of disease and correlates with cognitive symptoms. The pre-synaptic vesicle protein synaptotagmin-1 appears to be essential for the maintenance of an intact synaptic transmission and cognitive function. Synaptotagmin-1 in cerebrospinal fluid is a candidate Alzheimer biomarker for synaptic dysfunction that also may correlate with cognitive decline. METHODS: In this study, a novel mass spectrometry-based assay for measurement of cerebrospinal fluid synaptotagmin-1 was developed, and was evaluated in two independent sample sets of patients and controls...
October 3, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27701149/mst1-dependent-vesicle-trafficking-regulates-neutrophil-transmigration-through-the-vascular-basement-membrane
#12
Angela R M Kurz, Monika Pruenster, Ina Rohwedder, Mahalakshmi Ramadass, Kerstin Schäfer, Ute Harrison, Gabriel Gouveia, Claudia Nussbaum, Roland Immler, Johannes R Wiessner, Andreas Margraf, Dae-Sik Lim, Barbara Walzog, Steffen Dietzel, Markus Moser, Christoph Klein, Dietmar Vestweber, Rainer Haas, Sergio D Catz, Markus Sperandio
Neutrophils need to penetrate the perivascular basement membrane for successful extravasation into inflamed tissue, but this process is incompletely understood. Recent findings have associated mammalian sterile 20-like kinase 1 (MST1) loss of function with a human primary immunodeficiency disorder, suggesting that MST1 may be involved in immune cell migration. Here, we have shown that MST1 is a critical regulator of neutrophil extravasation during inflammation. Mst1-deficient (Mst1-/-) neutrophils were unable to migrate into inflamed murine cremaster muscle venules, instead persisting between the endothelium and the basement membrane...
November 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27687479/rab3a-and-rab10-are-regulators-of-lysosome-exocytosis-and-plasma-membrane-repair
#13
Otilia V Vieira
Disruption of the cell plasma membrane can occur due to mechanical damage, pore forming toxins, etc. Resealing or plasma membrane repair (PMR) is the emergency response required for cell survival. It is triggered by Ca(2+) entering through the disruption, causing organelles such as lysosomes located underneath the plasma membrane to fuse rapidly with the adjacent plasma membrane. We have recently identified some of the molecular traffic machinery that is involved in this vital process. Specifically, we showed that 2 members of the Rab family of small GTPases, Rab3a and Rab10, are essential for lysosome exocytosis and PMR in cells challenged with a bacterial toxin, streptolysin-O (SLO)...
September 29, 2016: Small GTPases
https://www.readbyqxmd.com/read/27666821/the-tobacco-specific-carcinogen-operated-calcium-channel-promotes-lung-tumorigenesis-via-igf2-exocytosis-in-lung-epithelial-cells
#14
Hye-Jin Boo, Hye-Young Min, Hyun-Ji Jang, Hye Jeong Yun, John Kendal Smith, Quanri Jin, Hyo-Jong Lee, Diane Liu, Hee-Seok Kweon, Carmen Behrens, J Jack Lee, Ignacio I Wistuba, Euni Lee, Waun Ki Hong, Ho-Young Lee
Nicotinic acetylcholine receptors (nAChRs) binding to the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces Ca(2+) signalling, a mechanism that is implicated in various human cancers. In this study, we investigated the role of NNK-mediated Ca(2+) signalling in lung cancer formation. We show significant overexpression of insulin-like growth factors (IGFs) in association with IGF-1R activation in human preneoplastic lung lesions in smokers. NNK induces voltage-dependent calcium channel (VDCC)-intervened calcium influx in airway epithelial cells, resulting in a rapid IGF2 secretion via the regulated pathway and thus IGF-1R activation...
2016: Nature Communications
https://www.readbyqxmd.com/read/27662292/aberrant-co-localization-of-synaptic-proteins-promoted-by-alzheimer-s-disease-amyloid-%C3%AE-peptides-protective-effect-of%C3%A2-human-serum-albumin
#15
Marta Domínguez-Prieto, Ana Velasco, Lourdes Vega, Arantxa Tabernero, José M Medina
Amyloid-β (Aβ), Aβ40, Aβ42, and, recently, Aβ25-35 have been directly implicated in the pathogenesis of Alzheimer's disease. We have studied the effects of Aβ on neuronal death, reactive oxygen species (ROS) production, and synaptic assembling in neurons in primary culture. Aβ25-35, Aβ40, and Aβ42 significantly decreased neuronal viability, although Aβ25-35 showed a higher effect. Aβ25-35 showed a more penetrating ability to reach mitochondria while Aβ40 did not enter the neuronal cytosol and Aβ42 was scarcely internalized...
November 1, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27660009/kai-xin-san-a-standardized-traditional-chinese-medicine-formula-up-regulates-the-expressions-of-synaptic-proteins-on-hippocampus-of-chronic-mild-stress-induced-depressive-rats-and-primary-cultured-rat-hippocampal-neuron
#16
Yue Zhu, Xiuzhu Duan, Xiaoxuan Cheng, Xiaonan Cheng, Xu Li, Liu Zhang, Pei Liu, Su Shulan, Jin-Ao Duan, Tina Ting-Xia Dong, Karl Wah-Keung Tsim, Fei Huang
BACKGROUND: Kai-xin-san (KXS), composed of Ginseng Radix et Rhizoma, Polygalae Radix, Acori Tatarinowii Rhizoma and Poria, is a famous Chinese medicinal formula applied for treating stress-related psychiatric disease with the symptoms such as depression, forgetfulness and dizziness. Dependent on the symptom differentiation of patients, the composition ratio of KXS was varied and one ratio of 3:2:2:3 was widely applied. However, its molecular mechanism has seldom been investigated. PURPOSE: We aimed to reveal the action mechanism of KXS on anti-depression on synaptic protein regulation in both in vivo and in vitro models...
September 19, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27658622/transport-of-a-kinesin-cargo-pair-along-microtubules-into-dendritic-spines-undergoing-synaptic-plasticity
#17
Derrick P McVicker, Adam M Awe, Karl E Richters, Rebecca L Wilson, Diana A Cowdrey, Xindao Hu, Edwin R Chapman, Erik W Dent
Synaptic plasticity often involves changes in the structure and composition of dendritic spines. Vesicular cargos and organelles enter spines either by exocytosing in the dendrite shaft and diffusing into spines or through a kinesin to myosin hand-off at the base of spines. Here we present evidence for microtubule (MT)-based targeting of a specific motor/cargo pair directly into hippocampal dendritic spines. During transient MT polymerization into spines, the kinesin KIF1A and an associated cargo, synaptotagmin-IV (syt-IV), are trafficked in unison along MTs into spines...
2016: Nature Communications
https://www.readbyqxmd.com/read/27650530/adenosine-a2a-receptor-and-ecto-5-nucleotidase-cd73-are-upregulated-in-hippocampal-astrocytes-of-human-patients-with-mesial-temporal-lobe-epilepsy-mtle
#18
Aurora R Barros-Barbosa, Fátima Ferreirinha, Ângela Oliveira, Marina Mendes, M Graça Lobo, Agostinho Santos, Rui Rangel, Julie Pelletier, Jean Sévigny, J Miguel Cordeiro, Paulo Correia-de-Sá
Refractoriness to existing medications of up to 80 % of the patients with mesial temporal lobe epilepsy (MTLE) prompts for finding new antiepileptic drug targets. The adenosine A2A receptor emerges as an interesting pharmacological target since its excitatory nature partially counteracts the dominant antiepileptic role of endogenous adenosine acting via inhibitory A1 receptors. Gain of function of the excitatory A2A receptor has been implicated in a significant number of brain pathologies commonly characterized by neuronal excitotoxicity...
September 20, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27624551/prrt2-from-paroxysmal-disorders-to-regulation-of-synaptic-function
#19
Flavia Valtorta, Fabio Benfenati, Federico Zara, Jacopo Meldolesi
In the past few years, proline-rich transmembrane protein (PRRT)2 has been identified as the causative gene for several paroxysmal neurological disorders. Recently, an important role of PRRT2 in synapse development and function has emerged. Knock down of the protein strongly impairs the formation of synaptic contacts and neurotransmitter release. At the nerve terminal, PRRT2 endows synaptic vesicle exocytosis with Ca(2+) sensitivity by interacting with proteins of the fusion complex and with the Ca(2+) sensors synaptotagmins (Syts)...
October 2016: Trends in Neurosciences
https://www.readbyqxmd.com/read/27609773/plexin-c1-deficiency-permits-synaptotagmin-7-mediated-macrophage-migration-and-enhances-mammalian-lung-fibrosis
#20
Xueyan Peng, Meagan Moore, Aditi Mathur, Yang Zhou, Huanxing Sun, Ye Gan, Jose D Herazo-Maya, Naftali Kaminski, Xinyuan Hu, Hongyi Pan, Changwan Ryu, Awo Osafo-Addo, Robert J Homer, Carol Feghali-Bostwick, Wassim H Fares, Mridu Gulati, Buqu Hu, Chun-Geun Lee, Jack A Elias, Erica L Herzog
Pulmonary fibrosis is a progressive and often fatal condition that is believed to be partially orchestrated by macrophages. Mechanisms that control migration of these cells into and within the lung remain undefined. We evaluated the contributions of the semaphorin receptor, plexin C1 (PLXNC1), and the exocytic calcium sensor, synaptotagmin 7 (Syt7), in these processes. We evaluated the role of PLXNC1 in macrophage migration by using Boyden chambers and scratch tests, characterized its contribution to experimentally induced lung fibrosis in mice, and defined the mechanism for our observations...
December 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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