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https://www.readbyqxmd.com/read/28202712/ribeye-b-domain-binds-to-lipid-components-of-synaptic-vesicles-in-an-nad-h-dependent-redox-sensitive-manner
#1
Karin Schwarz, Frank Schmitz
Synaptic ribbons are needed for fast and continuous exocytosis in ribbon synapses. RIBEYE is a main protein component of synaptic ribbons and necessary to build the synaptic ribbon. RIBEYE consists of a unique A-domain and a carboxyterminal B-domain that binds NAD(H). Within the presynaptic terminal, the synaptic ribbons are in physical contact with large numbers of synaptic vesicles. How this physical contact between ribbons and vesicles is established at a molecular level is not well understood. In the present study, we demonstrate that the RIBEYE(B)-domain can directly interact with lipid components of synaptic vesicles using two different sedimentation assays with liposomes of defined chemical composition...
February 15, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28198012/a-free-radical-approach-reveals-the-physiological-function-of-different-synaptic-vesicle-pools
#2
Michael A Cousin
No abstract text is available yet for this article.
February 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28197093/ultrastructural-and-functional-properties-of-a-giant-synapse-driving-the-piriform-cortex-to-mediodorsal-thalamus-projection
#3
Patric Pelzer, Heinz Horstmann, Thomas Kuner
Neocortico-thalamo-cortical loops represent a common, yet poorly understood, circuit employing giant synapses also referred to as "class I", giant, or driver synapses. Here, we characterize a giant synapse formed by projection neurons of the paleocortical piriform cortex (PIR) onto neurons of the mediodorsal thalamus (MD). Three-dimensional (3D) ultrastructure of labeled PIR-MD terminals, obtained by using serial-section scanning electron microscopy (EM) combined with photooxidation-based detection of labeled terminals, revealed a large terminal engulfing multiple postsynaptic dendritic excrescences...
2017: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/28193694/different-cav1-3-channel-isoforms-control-distinct-components-of-the-synaptic-vesicle-cycle-in-auditory-inner-hair-cells
#4
Philippe Fy Vincent, Yohan Bouleau, Gilles Charpentier, Alice Emptoz, Saaid Safieddine, Christine Petit, Didier Dulon
The mechanisms orchestrating transient and sustained exocytosis in auditory inner hair cells (IHCs) remain largely unknown. These exocytotic responses are believed to mobilize sequentially a readily releasable pool of vesicles (RRP) underneath the synaptic ribbons and a slowly releasable pool of vesicles (SRP) at farther distance from them. They are both governed by Cav1.3 channels and require otoferlin as Ca(2+) sensor but whether they use the same Cav1.3 isoforms is still unknown. Using whole cell patch clamp recordings in post-hearing mice, we show that only a proportion (∼25 %) of the total Ca(2+) current in IHCs, displaying fast inactivation and resistance to 20 μM nifedipine, a L-type Ca(2+) channel blocker, is sufficient to trigger RRP but not SRP exocytosis...
February 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28193235/dynamic-presenilin-1-and-synaptotagmin-1-interaction-modulates-exocytosis-and-amyloid-%C3%AE-production
#5
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/28192369/synaptic-unc13a-protein-variant-causes-increased-neurotransmission-and-dyskinetic-movement-disorder
#6
Noa Lipstein, Nanda M Verhoeven-Duif, Francesco E Michelassi, Nathaniel Calloway, Peter M van Hasselt, Katarzyna Pienkowska, Gijs van Haaften, Mieke M van Haelst, Ron van Empelen, Inge Cuppen, Heleen C van Teeseling, Annemieke M V Evelein, Jacob A Vorstman, Sven Thoms, Olaf Jahn, Karen J Duran, Glen R Monroe, Timothy A Ryan, Holger Taschenberger, Jeremy S Dittman, Jeong-Seop Rhee, Gepke Visser, Judith J Jans, Nils Brose
Munc13 proteins are essential regulators of neurotransmitter release at nerve cell synapses. They mediate the priming step that renders synaptic vesicles fusion-competent, and their genetic elimination causes a complete block of synaptic transmission. Here we have described a patient displaying a disorder characterized by a dyskinetic movement disorder, developmental delay, and autism. Using whole-exome sequencing, we have shown that this condition is associated with a rare, de novo Pro814Leu variant in the major human Munc13 paralog UNC13A (also known as Munc13-1)...
February 13, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28191772/human-induced-pluripotent-cell-derived-sensory-neurons-for-fate-commitment-of-bone-marrow-derived-schwann-cells-implications-for-remyelination-therapy
#7
Sa Cai, Lei Han, Qiang Ao, Ying-Shing Chan, Daisy Kwok-Yan Shum
Strategies that exploit induced pluripotent stem cells (iPSCs) to derive neurons have relied on cocktails of cytokines and growth factors to bias cell-signaling events in the course of fate choice. These are often costly and inefficient, involving multiple steps. In this study, we took an alternative approach and selected 5 small-molecule inhibitors of key signaling pathways in an 8-day program to induce differentiation of human iPSCs into sensory neurons, reaching ≥80% yield in terms of marker proteins. Continuing culture in maintenance medium resulted in neuronal networks immunopositive for synaptic vesicle markers and vesicular glutamate transporters suggestive of excitatory neurotransmission...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28188850/immunolocalization-of-the-vesicular-acetylcholine-transporter-in-larval-and-adult-drosophila-neurons
#8
Sridhar Boppana, Natalie Kendall, Opeyemi Akinrinsola, Daniel White, Krushali Patel, Hakeem Lawal
Vesicular acetylcholine transporter (VAChT) function is essential for organismal survival, mediating the packaging of acetylcholine (ACh) for exocytotic release. However, its expression pattern in the Drosophila brain has not been fully elucidated. To investigate the localization of VAChT, we developed an antibody against the C terminal region of the protein and we show that this antibody recognizes a 65KDa protein corresponding to VAChT on an immunoblot in both Drosophila head homogenates and in Schneider 2 cells...
February 7, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28188742/function-and-expression-of-a-splicing-variant-of-vesicular-glutamate-transporter-1
#9
Satomi Moriyama, Masafumi Iharada, Hiroshi Omote, Yoshinori Moriyama, Miki Hiasa
Vesicular glutamate transporter (VGLUT) is an active transporter responsible for vesicular storage of glutamate in synaptic vesicles and plays an essential role in glutamatergic neurotransmission. VGLUT consists of three isoforms, VGLUT1, VGLUT2, and VGLUT3. The VGLUT1 variant, VGLUT1v, with an additional 75-base pair sequence derived from a second intron between exons 2 and 3, which corresponds to 25 amino acid residues in the 1st loop of VGLUT1, is the only splicing variant among VGLUTs, although whether VGLUT1v protein is actually translated at the protein level remains unknown...
February 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28188302/vesicular-acetylcholine-transporter-defect-underlies-devastating-congenital-myasthenia-syndrome
#10
Adi Aran, Reeval Segel, Kota Kaneshige, Suleyman Gulsuner, Paul Renbaum, Scott Oliphant, Tomer Meirson, Ariella Weinberg-Shukron, Yair Hershkovitz, Sharon Zeligson, Ming K Lee, Abraham O Samson, Stanley M Parsons, Mary-Claire King, Ephrat Levy-Lahad, Tom Walsh
OBJECTIVE: To identify the genetic basis of a recessive congenital neurologic syndrome characterized by severe hypotonia, arthrogryposis, and respiratory failure. METHODS: Identification of the responsible gene by exome sequencing and assessment of the effect of the mutation on protein stability in transfected rat neuronal-like PC12(A123.7) cells. RESULTS: Two brothers from a nonconsanguineous Yemeni Jewish family manifested at birth with severe hypotonia and arthrogryposis...
February 10, 2017: Neurology
https://www.readbyqxmd.com/read/28186166/selective-molecular-impairment-of-spontaneous-neurotransmission-modulates-synaptic-efficacy
#11
Devon C Crawford, Denise M O Ramirez, Brent Trauterman, Lisa M Monteggia, Ege T Kavalali
Recent studies suggest that stimulus-evoked and spontaneous neurotransmitter release processes are mechanistically distinct. Here we targeted the non-canonical synaptic vesicle SNAREs Vps10p-tail-interactor-1a (vti1a) and vesicle-associated membrane protein 7 (VAMP7) to specifically inhibit spontaneous release events and probe whether these events signal independently of evoked release to the postsynaptic neuron. We found that loss of vti1a and VAMP7 impairs spontaneous high-frequency glutamate release and augments unitary event amplitudes by reducing postsynaptic eukaryotic elongation factor 2 kinase (eEF2K) activity subsequent to the reduction in N-methyl-D-aspartate receptor (NMDAR) activity...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28182901/one-cycle-fuels-another-the-energetics-of-neurotransmitter-release
#12
Katlin Silm, Robert H Edwards
In this issue of Neuron, Ashrafi et al. (2017) show that activity induces translocation of the insulin-regulated glucose transporter GLUT4 to the plasma membrane, where it sustains the ATP production required for synaptic vesicle cycling. However, translocation occurs from presynaptic membranes other than synaptic vesicles and involves a distinct molecular mechanism.
February 8, 2017: Neuron
https://www.readbyqxmd.com/read/28179460/vamp-7-dependent-secretion-at-the-immune-synapse-regulates-antigen-extraction-and-presentation-in-b-lymphocytes
#13
Dorian Obino, Jheimmy Diaz, Juan José Sáez, Jorge Ibañez-Vega, Pablo J Sáez, Martina Alamo, Danielle Lankar, Maria-Isabel Yuseff
Recognition of surface-tethered antigens (Ag) by B cells leads to the formation of an immune synapse that promotes Ag uptake for presentation onto MHC-II molecules. Extraction of immobilized antigens at the immune synapse of B cells relies on the local secretion of lysosomes, which are recruited to the antigen contact site by polarization of their microtubule network. Although conserved polarity proteins have been implicated in coordinating cytoskeleton remodeling with lysosome trafficking, the cellular machinery associated with lysosomal vesicles that regulates their docking and secretion at the synaptic interface has not been defined...
February 8, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28178198/zinc-transporter-3-znt3-in-the-enteric-nervous-system-of-the-porcine-ileum-in-physiological-conditions-and-during-experimental-inflammation
#14
Sławomir Gonkowski, Maciej Rowniak, Joanna Wojtkiewicz
Zinc transporter 3 (ZnT3) is a member of the solute-linked carrier 30 (SLC 30) zinc transporter family. It is closely linked to the nervous system, where it takes part in the transport of zinc ions from the cytoplasm to the synaptic vesicles. ZnT3 has also been observed in the enteric nervous system (ENS), but its reactions in response to pathological factors remain unknown. This study, based on the triple immunofluorescence technique, describes changes in ZnT3-like immunoreactive (ZnT3-LI) enteric neurons in the porcine ileum, caused by chemically-induced inflammation...
February 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28177287/mechanistic-insights-into-neurotransmitter-release-and-presynaptic-plasticity-from-the-crystal-structure-of-munc13-1-c1c2bmun
#15
Junjie Xu, Marcial Camacho, Yibin Xu, Vicotoria Esser, Xiaoxia Liu, Thorsten Trimbuch, Yun-Zu Pan, Cong Ma, Diana R Tomchick, Christian Rosenmund, Josep Rizo
Munc13-1 acts as a master regulator of neurotransmitter release, mediating docking-priming of synaptic vesicles and diverse presynaptic plasticity processes. It is unclear how the functions of the multiple domains of Munc13-1 are coordinated. The crystal structure of a Munc13-1 fragment including its C1, C2B and MUN domains (C1C2BMUN) reveals a 19.5 nm-long multi-helical structure with the C1 and C2B domains packed at one end. The similar orientations of the respective diacyglycerol- and Ca(2+)-binding sites of the C1 and C2B domains suggest that the two domains cooperate in plasma-membrane binding and that activation of Munc13-1 by Ca(2+) and diacylglycerol during short-term presynaptic plasticity are closely interrelated...
February 8, 2017: ELife
https://www.readbyqxmd.com/read/28168742/astrocyte-lipid-metabolism-is-critical-for-synapse-development-and-function-in-vivo
#16
Anne-Lieke F van Deijk, Nutabi Camargo, Jaap Timmerman, Tim Heistek, Jos F Brouwers, Floriana Mogavero, Huibert D Mansvelder, August B Smit, Mark H G Verheijen
The brain is considered to be autonomous in lipid synthesis with astrocytes producing lipids far more efficiently than neurons. Accordingly, it is generally assumed that astrocyte-derived lipids are taken up by neurons to support synapse formation and function. Initial confirmation of this assumption has been obtained in cell cultures, but whether astrocyte-derived lipids support synapses in vivo is not known. Here, we address this issue and determined the role of astrocyte lipid metabolism in hippocampal synapse formation and function in vivo...
February 7, 2017: Glia
https://www.readbyqxmd.com/read/28168212/novel-synaptobrevin-1-mutation-causes-fatal-congenital-myasthenic-syndrome
#17
Xin-Ming Shen, Rosana H Scola, Paulo J Lorenzoni, Cláudia S K Kay, Lineu C Werneck, Joan Brengman, Duygu Selcen, Andrew G Engel
OBJECTIVE: To identify the molecular basis and elucidate the pathogenesis of a fatal congenital myasthenic syndrome. METHODS: We performed clinical electrophysiology studies, exome and Sanger sequencing, and analyzed functional consequences of the identified mutation. RESULTS: Clinical electrophysiology studies of the patient revealed several-fold potentiation of the evoked muscle action potential by high frequency nerve stimulation pointing to a presynaptic defect...
February 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28165217/calcium-assists-dopamine-release-by-preventing-aggregation-on-the-inner-leaflet-of-presynaptic-vesicles
#18
Sini Mokkila, Pekka A Postila, Sami Rissanen, Hanna Juhola, Ilpo Vattulainen, Tomasz Rog
Tightly controlled neurotransmitter-membrane interactions can speed up signal transduction by coordinating the movements of the transmitters inside the synapse. In this study, the dopamine-lipid bilayer interactions were probed with three physiologically relevant ion compositions using atomistic molecular dynamics simulations and free energy calculations. The in silico results show that calcium decreases significantly the binding of dopamine to a neutral (zwitterionic) phosphatidylcholine lipid bilayer used to model the inner leaflet of a presynaptic vesicle...
February 6, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28163913/where-does-axon-guidance-lead-us
#19
REVIEW
Esther Stoeckli
During neural circuit formation, axons need to navigate to their target cells in a complex, constantly changing environment. Although we most likely have identified most axon guidance cues and their receptors, we still cannot explain the molecular background of pathfinding for any subpopulation of axons. We lack mechanistic insight into the regulation of interactions between guidance receptors and their ligands. Recent developments in the field of axon guidance suggest that the regulation of surface expression of guidance receptors comprises transcriptional, translational, and post-translational mechanisms, such as trafficking of vesicles with specific cargos, protein-protein interactions, and specific proteolysis of guidance receptors...
2017: F1000Research
https://www.readbyqxmd.com/read/28163686/the-multifaceted-role-of-snare-proteins-in-membrane-fusion
#20
REVIEW
Jing Han, Kristyna Pluhackova, Rainer A Böckmann
Membrane fusion is a key process in all living organisms that contributes to a variety of biological processes including viral infection, cell fertilization, as well as intracellular transport, and neurotransmitter release. In particular, the various membrane-enclosed compartments in eukaryotic cells need to exchange their contents and communicate across membranes. Efficient and controllable fusion of biological membranes is known to be driven by cooperative action of SNARE proteins, which constitute the central components of the eukaryotic fusion machinery responsible for fusion of synaptic vesicles with the plasma membrane...
2017: Frontiers in Physiology
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