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https://www.readbyqxmd.com/read/28097727/energetics-kinetics-and-pathway-of-snare-folding-and-assembly-revealed-by-optical-tweezers
#1
REVIEW
Yongli Zhang
Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are universal molecular engines that drive membrane fusion. Particularly, synaptic SNAREs mediate fast calcium-triggered fusion of neurotransmitter-containing vesicles with plasma membranes for synaptic transmission, the basis of all thought and action. During membrane fusion, complementary SNAREs located on two apposed membranes (often called t- and v-SNAREs) join together to assemble into a parallel four-helix bundle, releasing the energy to overcome the energy barrier for fusion...
January 18, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28093477/differential-presynaptic-atp-supply-for-basal-and-high-demand-transmission
#2
Courtney Sobieski, Michael J Fitzpatrick, Steven Mennerick
The relative contributions of glycolysis and oxidative phosphorylation to neuronal presynaptic energy demands are unclear. In rat hippocampal neurons, ATP production by either glycolysis or oxidative phosphorylation alone sustained basal evoked synaptic transmission for up to 20 min. However, combined inhibition of both ATP sources abolished evoked transmission. Neither action potential propagation failure nor depressed Ca(2+)-influx explained loss of evoked synaptic transmission. Rather, inhibition of ATP synthesis caused massive spontaneous vesicle exocytosis, followed by arrested endocytosis, accounting for the disappearance of evoked postsynaptic currents (PSCs)...
January 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28089870/large-dense-core-vesicle-exocytosis-from-mouse-dorsal-root-ganglion-neurons-is-regulated-by-neuropeptide-y
#3
Anneka Bost, Ali H Shaib, Yvonne Schwarz, Barbara A Niemeyer, Ute Becherer
Peptidergic dorsal root ganglion (DRG) neurons transmit sensory and nociceptive information from the periphery to the central nervous system. Their synaptic activity is profoundly affected by neuromodulatory peptides stored and released from large dense-core vesicles (LDCVs). However, the mechanism of peptide secretion from DRG neurons is poorly understood. Using total internal reflection fluorescence microscopy (TIRFM), we visualized individual LDCVs loaded with fluorescent neuropeptide Y (NPY) and analyzed their stimulation-dependent release...
January 12, 2017: Neuroscience
https://www.readbyqxmd.com/read/28087765/synapsin-ii-regulation-of-gabaergic-synaptic-transmission-is-dependent-on-interneuron-subtype
#4
Pedro Feliciano, Heidi Matos, Rodrigo Andrade, Maria Bykhovskaia
: Synapsins are epilepsy susceptibility genes that encode phosphoproteins reversibly associated with synaptic vesicles. Synapsin II (SynII) gene deletion produces a deficit in inhibitory synaptic transmission, and this defect is thought to cause epileptic activity. We systematically investigated how SynII affects synchronous and asynchronous release components of inhibitory transmission in the CA1 region of the mouse hippocampus. We found that the asynchronous GABAergic release component is diminished in SynII deleted (SynII(-)) slices...
January 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28086931/the-release-and-trans-synaptic-transmission-of-tau-via-exosomes
#5
Yipeng Wang, Varun Balaji, Senthilvelrajan Kaniyappan, Lars Krüger, Stephan Irsen, Katharina Tepper, RamReddy Chandupatla, Walter Maetzler, Anja Schneider, Eckhard Mandelkow, Eva-Maria Mandelkow
BACKGROUND: Tau pathology in AD spreads in a hierarchical pattern, whereby it first appears in the entorhinal cortex, then spreads to the hippocampus and later to the surrounding areas. Based on this sequential appearance, AD can be classified into six stages ("Braak stages"). The mechanisms and agents underlying the progression of Tau pathology are a matter of debate. Emerging evidence indicates that the propagation of Tau pathology may be due to the transmission of Tau protein, but the underlying pathways and Tau species are not well understood...
January 13, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28077717/complexin-mutants-reveal-partial-segregation-between-recycling-pathways-that-drive-evoked-and-spontaneous-neurotransmission
#6
Nadezhda Sabeva, Richard W Cho, Alexander Vasin, Agustin Gonzalez, J Troy Littleton, Maria Bykhovskaia
: Synaptic vesicles fuse at morphological specializations in the presynaptic terminal termed active zones (AZs). Vesicle fusion can occur spontaneously or in response to an action potential. Following fusion, vesicles are retrieved and recycled within nerve terminals. It is still unclear whether vesicles that fuse spontaneously or following evoked release share similar recycling mechanisms. Genetic deletion of the SNARE-binding protein complexin dramatically increases spontaneous fusion, with the protein serving as the synaptic vesicle fusion clamp at Drosophila synapses...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28071723/hcn1-channels-reduce-the-rate-of-exocytosis-from-a-subset-of-cortical-synaptic-terminals
#7
Zhuo Huang, Gengyu Li, Carolina Aguado, Rafael Lujan, Mala M Shah
The hyperpolarization-activated cyclic nucleotide-gated (HCN1) channels are predominantly located in pyramidal cell dendrites within the cortex. Recent evidence suggests these channels also exist pre-synaptically in a subset of synaptic terminals within the mature entorhinal cortex (EC). Inhibition of pre-synaptic HCN channels enhances miniature excitatory post-synaptic currents (mEPSCs) onto EC layer III pyramidal neurons, suggesting that these channels decrease the release of the neurotransmitter, glutamate...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28067523/increased-binding-of-calcium-ions-at-positively-curved-phospholipid-membranes
#8
Aniket Magarkar, Piotr Jurkiewicz, Christoph Allolio, Martin Hof, Pavel Jungwirth
Calcium ion is the ubiquitous messenger in cells and plays a key role in neuronal signaling and fusion of synaptic vesicles. These vesicles are typically ∼20-50 nm in diameter, and thus their interaction with calcium ions cannot be modeled faithfully with a conventional flat membrane bilayer setup. Within our newly developed molecular dynamics simulations setup, we characterize here interactions of the calcium ion with curved membrane interfaces with atomistic detail. The present molecular dynamics simulations together with time-dependent fluorescence shift experiments suggest that the mode and strength of interaction of calcium ion with a phospholipid bilayer depends on its curvature...
January 19, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28065609/sexually-dimorphic-differentiation-of-a-c-%C3%A2-elegans-hub-neuron-is-cell-autonomously-controlled-by-a-conserved-transcription-factor
#9
Esther Serrano-Saiz, Meital Oren-Suissa, Emily A Bayer, Oliver Hobert
Functional and anatomical sexual dimorphisms in the brain are either the result of cells that are generated only in one sex or a manifestation of sex-specific differentiation of neurons present in both sexes. The PHC neuron pair of the nematode C. elegans differentiates in a strikingly sex-specific manner. In hermaphrodites the PHC neurons display a canonical pattern of synaptic connectivity similar to that of other sensory neurons, but in males PHC differentiates into a densely connected hub sensory neuron/interneuron, integrating a large number of male-specific synaptic inputs and conveying them to both male-specific and sex-shared circuitry...
January 2, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28059803/whole-body-vibration-wbv-following-spinal-cord-injury-sci-in-rats-timing-of-intervention
#10
Marilena Manthou, Diana Saad Yousif Abdulla, Stoyan Pavlov Pavlov, Ramona Jansen, Habib Bendella, Klaus Nohroudi, Gregor Stein, Carolin Mmeyer, Ozlem Ozsoy, Umut Ozsoy, Yasemin Behram Kandemir, Levent Sarikcioglu, Oliver Semler, Eckhard Schoenau, Sarah Dunlop, Doychin Nikolov Angelov
BACKGROUND: Following spinal cord injury (SCI), exercise training provides a wide range of benefits and promotes activity-dependent synaptic plasticity. Whole body vibration (WBV) in SCI patients improves walking and spasticity as well as bone and muscle mass. However, little is known about the effects of timing or frequency of intervention. OBJECTIVE: To determine which WBV-onset improves locomotor and bladder functions and influences synaptic plasticity beneficially...
January 4, 2017: Restorative Neurology and Neuroscience
https://www.readbyqxmd.com/read/28057568/localization-of-rab3a-binding-site-on-c2a-domain-of-synaptotagmin-i-to-reveal-its-regulatory-mechanism
#11
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/28057534/altered-fronto-striatal-functions-in-the-gdi1-null-mouse-model-of-x-linked-intellectual-disability
#12
Lorenzo Morè, Basil Künnecke, Latefa Yekhlef, Andreas Bruns, Antonella Marte, Ernesto Fedele, Veronica Bianchi, Stefano Taverna, Silvia Gatti, Patrizia D'Adamo
RAB-GDP dissociation inhibitor 1 (GDI1) loss-of-function mutations are responsible for a form of non-specific X-linked Intellectual Disability (XLID) where the only clinical feature is cognitive impairment. GDI1 patients are impaired in specific aspects of executive functions and conditioned response, which are controlled by fronto-striatal circuitries. Previous molecular and behavioral characterization of the Gdi1-null mouse revealed alterations in the total number/distribution of hippocampal and cortical synaptic vesicles as well as hippocampal short-term synaptic plasticity, and memory deficits...
January 3, 2017: Neuroscience
https://www.readbyqxmd.com/read/28057533/presynaptic-pick1-facilitates-trafficking-of-ampa-receptors-between-active-zone-and-synaptic-vesicle-pool
#13
C Haglerød, S Hussain, Y Nakamura, J Xia, F M Haug, O P Ottersen, J M Henley, S Davanger
Previous studies have indicated that presynaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) contribute to the regulation of neurotransmitter release. In hippocampal synapses, the presynaptic surface expression of several AMPAR subunits, including GluA2, is regulated in a ligand-dependent manner. However, the molecular mechanisms underlying the presynaptic trafficking of AMPARs are still unknown. Here, using bright-field immunocytochemistry, western blots, and quantitative immunogold electron microscopy of the hippocampal CA1 area from intact adult rat brain, we demonstrate the association of AMPA receptors with the presynaptic active zone and with small presynaptic vesicles, in Schaffer collateral synapses in CA1 of the hippocampus...
January 3, 2017: Neuroscience
https://www.readbyqxmd.com/read/28056033/fiji-macro-3d-art-veselect-3d-automated-reconstruction-tool-for-vesicle-structures-of-electron-tomograms
#14
Kristin Verena Kaltdorf, Katja Schulze, Frederik Helmprobst, Philip Kollmannsberger, Thomas Dandekar, Christian Stigloher
Automatic image reconstruction is critical to cope with steadily increasing data from advanced microscopy. We describe here the Fiji macro 3D ART VeSElecT which we developed to study synaptic vesicles in electron tomograms. We apply this tool to quantify vesicle properties (i) in embryonic Danio rerio 4 and 8 days past fertilization (dpf) and (ii) to compare Caenorhabditis elegans N2 neuromuscular junctions (NMJ) wild-type and its septin mutant (unc-59(e261)). We demonstrate development-specific and mutant-specific changes in synaptic vesicle pools in both models...
January 5, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28054433/insertion-of-neurotransmitters-into-lipid-bilayer-membrane-and-its-implication-on-membrane-stability-a-molecular-dynamics-study
#15
Chun Shen, Minmin Xue, Hu Qiu, Wanlin Guo
The signaling molecules in neuron called neurotransmitters play an essential role in transportation of neural signal, during which the neurotransmitters interact with not only specific receptors but also cytomembranes such as synaptic vesicle membranes and postsynaptic membranes. Here we investigate by extensive molecular dynamics simulations the atomic-scale insertion dynamics of typical neurotransmitters, including methionine enkephalin (ME), leucine enkephalin (LE), dopamine (DA), acetylcholine (ACh) and aspartic acid (ASP), into lipid bilayers...
January 5, 2017: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://www.readbyqxmd.com/read/28052246/synucleins-have-multiple-effects-on-presynaptic-architecture
#16
Karina J Vargas, Nikolas Schrod, Taylor Davis, Ruben Fernandez-Busnadiego, Yumiko V Taguchi, Ulrike Laugks, Vladan Lucic, Sreeganga S Chandra
Synucleins (α, β, γ-synuclein) are a family of abundant presynaptic proteins. α-Synuclein is causally linked to the pathogenesis of Parkinson's disease (PD). In an effort to define their physiological and pathological function or functions, we investigated the effects of deleting synucleins and overexpressing α-synuclein PD mutations, in mice, on synapse architecture using electron microscopy (EM) and cryoelectron tomography (cryo-ET). We show that synucleins are regulators of presynapse size and synaptic vesicle (SV) pool organization...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28049811/measuring-the-basic-physiological-properties-of-synapses
#17
Matthew A Xu-Friedman
Studying synaptic physiology remains an important endeavor for understanding the mechanisms that underlie neurotransmitter release as well as synaptic development and refinement. It is also critical to understanding brain function. The basic conceptual framework for synaptic physiology was worked out by Katz and colleagues and has coalesced around three factors: the number of releasable vesicles (N), the probability of release (P), and quantal size (Q). Here, I discuss a few key experiments related to these quantities and how they are assessed...
January 3, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/28041965/analysis-of-gene-expression-in-ca-2-dependent-activator-protein-for-secretion-2-cadps2-knockout-cerebellum-using-genechip-and-kegg-pathways
#18
Tetsushi Sadakata, Yo Shinoda, Yasuki Ishizaki, Teiichi Furuichi
In the mouse cerebellum, Ca(2+)-dependent activator protein for secretion 2 (CADPS2, CAPS2) is involved in regulated secretion from dense-core vesicles (DCVs), which contain neuropeptides including brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). Capds2 knockout (KO) mice show impaired cerebellar development in addition to autistic-like behavioral phenotypes. To understand the molecular impact caused by loss of Capds2, we analyzed gene expression profiles in the Capds2 KO cerebellum using a GeneChip microarray and the KEGG Pathway database...
December 29, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/28039330/dissecting-the-influence-of-two-structural-substituents-on-the-differential-neurotoxic-effects-of-methamphetamine-and-mephedrone-on-dopamine-nerve-endings-with-the-use-of-4-methylmethamphetamine-and-methcathinone
#19
John H Anneken, Mariana Angoa-Perez, Girish C Sati, David Crich, Donald M Kuhn
Mephedrone (MEPH) is a β-ketoamphetamine stimulant drug of abuse that is often a constituent of illicit bath salts formulations. While MEPH bears remarkable similarities to methamphetamine (METH) in terms of chemical structure, as well as its neurochemical and behavioral effects, it has been shown to have a reduced neurotoxic profile compared to METH. The addition of a β-keto moiety and a 4-methyl ring substituent to METH yields MEPH, and a loss of direct neurotoxic potential. In the present study, 2 analogs of METH, methcathinone (MeCa) and 4-methylmethamphetamine (4MM), were assessed for their effects on mouse dopamine (DA) nerve endings to determine the relative contribution of each individual moiety to the loss of direct neurotoxicity in MEPH...
December 30, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28035046/the-pleckstrin-homology-domain-of-dynamin-is-dispensable-for-membrane-constriction-and-fission
#20
Srishti Dar, Thomas J Pucadyil
Classical dynamins bind the plasma membrane-localized phosphatidylinositol-4,5-bisphosphate using the pleckstrin-homology domain (PHD) and engage in rapid membrane fission during synaptic vesicle recycling. This domain is conspicuously absent among extant bacterial and mitochondrial dynamins, however, where loop regions manage membrane recruitment. Inspired by the core design of bacterial and mitochondrial dynamins, we reengineered the classical dynamin by replacing its PHD with a polyhistidine or polylysine linker...
January 1, 2017: Molecular Biology of the Cell
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