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Synaptic vesicle

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https://www.readbyqxmd.com/read/28917663/leucine-rich-%C3%AE-2-glycoprotein-overexpression-in-the-brain-contributes-to-memory-impairment
#1
Chihiro Akiba, Madoka Nakajima, Masakazu Miyajima, Ikuko Ogino, Masami Miura, Ritsuko Inoue, Eri Nakamura, Fumio Kanai, Norihiro Tada, Miyuki Kunichika, Mitsutaka Yoshida, Kinya Nishimura, Akihide Kondo, Hidenori Sugano, Hajime Arai
We previously reported increase in leucine-rich α2-glycoprotein (LRG) concentration in cerebrospinal fluid is associated with cognitive decline in humans. To investigate relationship between LRG expression in the brain and memory impairment, we analyzed transgenic mice overexpressing LRG in the brain (LRG-Tg) focusing on hippocampus. Immunostaining and Western blotting revealed age-related increase in LRG expression in hippocampal neurons in 8-, 24-, and 48-week-old controls and LRG-Tg. Y-maze and Morris water maze tests indicated retained spatial memory in 8- and 24-week-old LRG-Tg, while deteriorated in 48-week-old LRG-Tg compared with age-matched controls...
August 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28912692/calsyntenins-are-expressed-in-a-dynamic-and-partially-overlapping-manner-during-neural-development
#2
Gemma de Ramon Francàs, Tobias Alther, Esther T Stoeckli
Calsyntenins form a family of linker proteins between distinct populations of vesicles and kinesin motors for axonal transport. They were implicated in synapse formation and synaptic plasticity by findings in worms, mice and humans. These findings were in accordance with the postsynaptic localization of the Calsyntenins in the adult brain. However, they also affect the formation of neural circuits, as loss of Calsyntenin-1 (Clstn1) was shown to interfere with axonal branching and axon guidance. Despite the fact that Calsyntenins were discovered originally in embryonic chicken motoneurons, their distribution in the developing nervous system has not been analyzed in detail so far...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28904098/characterization-of-ion-channels-and-o2-sensitivity-in-gill-neuroepithelial-cells-of-the-anoxia-tolerant-goldfish-carassius-auratus
#3
Peter C Zachar, Wen Pan, Michael G Jonz
The neuroepithelial cell (NEC) of the fish gill is an important model for O2 sensing in vertebrates; however, a complete picture of the chemosensory mechanisms in NECs is lacking, and O2 chemoreception in vertebrates that are tolerant to anoxia has yet not been explored. Using whole-cell patch-clamp recording, we characterized four types of ion channels in NECs isolated from the anoxia-tolerant goldfish. A Ca(2+)-dependent K(+) current (IKCa) peaked at ~20 mV, was potentiated by increased intracellular Ca(2+), and was reduced by 100 μM Cd(2+) A voltage-dependent inward current in Ba(2+) solution, with peak at 0 mV, confirmed the presence of Ca(2+) channels...
September 13, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28895532/a-synaptotagmin-suppressor-screen-indicates-snare-binding-controls-the-timing-and-ca-2-cooperativity-of-vesicle-fusion
#4
Zhuo Guan, Maria Bykhovskaia, Ramon A Jorquera, Roger Bryan Sutton, Yulia Akbergenova, J Troy Littleton
The synaptic vesicle Ca(2+) sensor Synaptotagmin binds Ca(2+) through its two C2 domains to trigger membrane interactions. Beyond membrane insertion by the C2 domains, other requirements for Synaptotagmin activity are still being elucidated. To identify key residues within Synaptotagmin required for vesicle cycling, we took advantage of observations that mutations in the C2B domain Ca(2+)-binding pocket dominantly disrupt release from invertebrates to humans. We performed an intragenic screen for suppressors of lethality induced by expression of Synaptotagmin C2B Ca(2+)-binding mutants in Drosophila...
September 12, 2017: ELife
https://www.readbyqxmd.com/read/28892038/measuring-synaptic-vesicle-endocytosis-in-cultured-hippocampal-neurons
#5
Seth Villarreal, Sung Hoon Lee, Ling-Gang Wu
During endocytosis, fused synaptic vesicles are retrieved at nerve terminals, allowing for vesicle recycling and thus the maintenance of synaptic transmission during repetitive nerve firing. Impaired endocytosis in pathological conditions leads to decreases in synaptic strength and brain functions. Here, we describe methods used to measure synaptic vesicle endocytosis at the mammalian hippocampal synapse in neuronal culture. We monitored synaptic vesicle protein endocytosis by fusing a synaptic vesicular membrane protein, including synaptophysin and VAMP2/synaptobrevin, at the vesicular lumenal side, with pHluorin, a pH-sensitive green fluorescent protein that increases its fluorescence intensity as the pH increases...
September 4, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28887876/cell-specific-gain-modulation-by-synaptically-released-zinc-in-cortical-circuits-of-audition
#6
Charles T Anderson, Manoj Kumar, Shanshan Xiong, Thanos Tzounopoulos
In many excitatory synapses, mobile zinc is found within glutamatergic vesicles and is coreleased with glutamate. Ex vivo studies established that synaptically released (synaptic) zinc inhibits excitatory neurotransmission at lower frequencies of synaptic activity but enhances steady state synaptic responses during higher frequencies of activity. However, it remains unknown how synaptic zinc affects neuronal processing in vivo. Here, we imaged the sound-evoked neuronal activity of the primary auditory cortex in awake mice...
September 9, 2017: ELife
https://www.readbyqxmd.com/read/28887593/v-snare-function-in-chromaffin-cells
#7
REVIEW
Madhurima Dhara, Ralf Mohrmann, Dieter Bruns
Vesicle fusion is elementary for intracellular trafficking and release of signal molecules, thus providing the basis for diverse forms of intercellular communication like hormonal regulation or synaptic transmission. A detailed characterization of the mechanisms underlying exocytosis is key to understand how the nervous system integrates information and generates appropriate responses to stimuli. The machinery for vesicular release employs common molecular players in different model systems including neuronal and neuroendocrine cells, in particular members of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) protein family, Sec1/Munc18-like proteins, and other accessory factors...
September 8, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28887151/altered-synaptobrevin-ii-trafficking-in-neurons-expressing-a-synaptophysin-mutation-associated-with-a-severe-neurodevelopmental-disorder
#8
Callista B Harper, Grazia M S Mancini, Marjon van Slegtenhorst, Michael A Cousin
Following exocytosis, synaptic vesicles (SVs) have to be reformed with the correct complement of proteins in the correct stoichiometry to ensure continued neurotransmission. Synaptophysin is a highly abundant, integral SV protein necessary for the efficient retrieval of the SV SNARE protein, synaptobrevin II (sybII). However the molecular mechanism underpinning synaptophysin-dependent sybII retrieval is still unclear. We recently identified a male patient with severe intellectual disability, hypotonia, epilepsy and callosal agenesis who has a point mutation in the juxtamembrane region of the fourth transmembrane domain of synaptophysin (T198I)...
September 5, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28884437/extrapolation-of-a-brivaracetam-exposure-response-model-from-adults-to-children-with-focal-seizures
#9
Rik Schoemaker, Janet R Wade, Armel Stockis
INTRODUCTION: Prediction of brivaracetam effects in children was obtained by scaling an existing adult pharmacokinetic/pharmacodynamic (PK/PD) model for brivaracetam to children, using an existing population PK model for brivaracetam in children. The scaling was supported by estimating the change from adults to children in the concentration-effect relationship parameters for levetiracetam, a compound interacting with the same target protein (synaptic vesicle protein SV2A). METHODS: The existing adult PK/PD model for brivaracetam was applied to a combined adult-pediatric dataset of levetiracetam...
September 7, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28883501/caps-1-requires-its-c2-ph-mhd1-and-dcv-domains-for-dense-core-vesicle-exocytosis-in-mammalian-cns-neurons
#10
Linda van Keimpema, Robbelien Kooistra, Ruud F Toonen, Matthijs Verhage
CAPS (calcium-dependent activator protein for secretion) are multi-domain proteins involved in regulated exocytosis of synaptic vesicles (SVs) and dense core vesicles (DCVs). Here, we assessed the contribution of different CAPS-1 domains to its subcellular localization and DCV exocytosis by expressing CAPS-1 mutations in four functional domains in CAPS-1/-2 null mutant (CAPS DKO) mouse hippocampal neurons, which are severely impaired in DCV exocytosis. CAPS DKO neurons showed normal development and no defects in DCV biogenesis and their subcellular distribution...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28882990/extended-synaptotagmin-localizes-to-presynaptic-er-and-promotes-neurotransmission-and-synaptic-growth-in-drosophila
#11
Koto Kikuma, Xiling Li, Daniel Kim, David Sutter, Dion K Dickman
The endoplasmic reticulum (ER) is an extensive organelle in neurons with important roles at synapses including the regulation of cytosolic Ca(2+), neurotransmission, lipid metabolism, and membrane trafficking. Despite intriguing evidence for these crucial functions, how presynaptic ER influences synaptic physiology remains enigmatic. To gain insight into this question, we have generated and characterized mutations in the single Extended Synaptotagmin (Esyt) ortholog in Drosophila melanogaster Esyts are evolutionarily conserved ER proteins with Ca(2+)-sensing domains that have recently been shown to orchestrate membrane tethering and lipid exchange between the ER and plasma membrane...
September 7, 2017: Genetics
https://www.readbyqxmd.com/read/28880475/recent-new-insights-into-the-role-of-snare-and-associated-proteins-in-insulin-granule-exocytosis
#12
REVIEW
Herbert Y Gaisano
Initial work on the exocytotic machinery of predocked insulin secretory granules (SGs) in pancreatic β-cells mimicked the SNARE hypothesis work in neurons, which includes SM/SNARE complex and associated priming proteins, fusion clamps and Ca(2+) sensors. However, β-cell SGs, unlike neuronal synaptic vesicles, exhibit a biphasic secretory response that requires additional distinct features in exocytosis including newcomer SGs that undergo minimal docking time at the plasma membrane (PM) before fusion and multi-SG (compound) fusion...
September 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28878621/the-networks-of-genes-encoding-palmitoylated-proteins-in-axonal-and-synaptic-compartments-are-affected-in-ppt1-overexpressing-neuronal-like-cells
#13
Francesco Pezzini, Marzia Bianchi, Salvatore Benfatto, Francesca Griggio, Stefano Doccini, Rosalba Carrozzo, Arvydas Dapkunas, Massimo Delledonne, Filippo M Santorelli, Maciej M Lalowski, Alessandro Simonati
CLN1 disease (OMIM #256730) is an early childhood ceroid-lipofuscinosis associated with mutated CLN1, whose product Palmitoyl-Protein Thioesterase 1 (PPT1) is a lysosomal enzyme involved in the removal of palmitate residues from S-acylated proteins. In neurons, PPT1 expression is also linked to synaptic compartments. The aim of this study was to unravel molecular signatures connected to CLN1. We utilized SH-SY5Y neuroblastoma cells overexpressing wild type CLN1 (SH-p.wtCLN1) and five selected CLN1 patients' mutations...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28875026/segregation-of-lipids-near-acetylcholine-receptor-channels-imaged-by-cryo-em
#14
Nigel Unwin
Rapid communication at the chemical synapse depends on the action of ion channels residing in the postsynaptic membrane. The channels open transiently upon the binding of a neurotransmitter released from the presynaptic nerve terminal, eliciting an electrical response. Membrane lipids also play a vital but poorly understood role in this process of synaptic transmission. The present study examines the lipid distribution around nicotinic acetylcholine (ACh) receptors in tubular vesicles made from postsynaptic membranes of the Torpedo ray, taking advantage of the recent advances in cryo-EM...
July 1, 2017: IUCrJ
https://www.readbyqxmd.com/read/28874522/efficient-stimulus-secretion-coupling-at-ribbon-synapses-requires-rim-binding-protein-tethering-of-l-type-ca-2-channels
#15
Fujun Luo, Xinran Liu, Thomas C Südhof, Claudio Acuna
Fast neurotransmitter release from ribbon synapses via Ca(2+)-triggered exocytosis requires tight coupling of L-type Ca(2+) channels to release-ready synaptic vesicles at the presynaptic active zone, which is localized at the base of the ribbon. Here, we used genetic, electrophysiological, and ultrastructural analyses to probe the architecture of ribbon synapses by perturbing the function of RIM-binding proteins (RBPs) as central active-zone scaffolding molecules. We found that genetic deletion of RBP1 and RBP2 did not impair synapse ultrastructure of ribbon-type synapses formed between rod bipolar cells (RBCs) and amacrine type-2 (AII) cells in the mouse retina but dramatically reduced the density of presynaptic Ca(2+) channels, decreased and desynchronized evoked neurotransmitter release, and rendered evoked and spontaneous neurotransmitter release sensitive to the slow Ca(2+) buffer EGTA...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28873406/estimating-short-term-synaptic-plasticity-from-pre-and-postsynaptic-spiking
#16
Abed Ghanbari, Aleksey Malyshev, Maxim Volgushev, Ian H Stevenson
Short-term synaptic plasticity (STP) critically affects the processing of information in neuronal circuits by reversibly changing the effective strength of connections between neurons on time scales from milliseconds to a few seconds. STP is traditionally studied using intracellular recordings of postsynaptic potentials or currents evoked by presynaptic spikes. However, STP also affects the statistics of postsynaptic spikes. Here we present two model-based approaches for estimating synaptic weights and short-term plasticity from pre- and postsynaptic spike observations alone...
September 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28873252/carbonic-anhydrase-inhibitor-acetazolamide-shifts-synaptic-vesicle-recycling-to-a-fast-mode-at-the-mouse-neuromuscular-junction
#17
Nicolas Ivan Bertone, Ayelén Ivana Groisman, Graciela Lujan Mazzone, Raquel Cano, Lucia Tabares, Osvaldo Daniel Uchitel
Acetazolamide (AZ), a molecule frequently used to treat different neurological syndromes, is an inhibitor of the carbonic anhydrase (CA), an enzyme that regulates pH inside and outside cells. We combined fluorescent FM styryl dyes and electrophysiological techniques at ex vivo levator auris longus neuromuscular junctions (NMJs) from mice to investigate the modulation of synaptic transmission and vesicle recycling by AZ. Transmitter release was minimally affected by AZ, as evidenced by evoked and spontaneous end-plate potential measurements...
September 5, 2017: Synapse
https://www.readbyqxmd.com/read/28871168/central-nervous-system-responses-of-the-oriental-migratory-locusta-migratoria-manilensis-to-fungal-infection
#18
Wei Zhang, Jianhong Chen, Nemat O Keyhani, Kai Jin, Qinlv Wei, Yuxian Xia
Responses of the central nervous system (CNS) to microbial challenge and the interplay between the CNS and the immune system are important for defending against pathogen attack. We have examined the CNS transcriptional response of Locusta migratoria manilensis to infection by the locust-specific fungal pathogen, Metarhizium acridum. CNS responses were examined during spore attachment, fungal germination and pre-penetration of the cuticle, and cuticle penetration/hemocoel ingress and proliferation. Effects were seen at the earliest time points (4 h post-infection) and the number of differentially expressed genes (DEGs) was highest during late mycosis (72 h post-infection)...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28871036/sodium-channel-%C3%AE-2-subunits-prevent-action-potential-propagation-failures-at-axonal-branch-points
#19
In Ha Cho, Lauren C Panzera, Morven Chin, Michael B Hoppa
Neurotransmitter release depends on voltage-gated Na(+) channels (Navs) to successfully propagate an action potential (AP) from the axon hillock to a synaptic terminal. Unmyelinated sections of axon are very diverse structures encompassing branch points and numerous presynaptic terminals with undefined molecular partners of Na(+) channels. Using optical recordings of Ca(2+) and membrane voltage, we demonstrate that Na(+) channel β2 subunits (Navβ2) are required to prevent AP propagation failures across the axonal arborization of cultured rat hippocampal neurons (mixed male and female)...
September 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28869469/trehalose-improves-cognition-in-the-transgenic-tg2576-mouse-model-of%C3%A2-alzheimer-s-disease
#20
Stuart D Portbury, Dominic J Hare, Charlotte Sgambelloni, Kali Perronnes, Ashley J Portbury, David I Finkelstein, Paul A Adlard
This study assessed the therapeutic utility of the autophagy enhancing stable disaccharide trehalose in the Tg2576 transgenic mouse model of Alzheimer's disease (AD) via an oral gavage of a 2% trehalose solution for 31 days. Furthermore, as AD is a neurodegenerative condition in which the transition metals, iron, copper, and zinc, are understood to be intricately involved in the cellular cascades leading to the defining pathologies of the disease, we sought to determine any parallel impact of trehalose treatment on metal levels...
August 30, 2017: Journal of Alzheimer's Disease: JAD
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