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      SynProt: A Database for Proteins of Detergent-Resistant Synaptic Protein Preparations

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          Abstract

          Chemical synapses are highly specialized cell–cell contacts for communication between neurons in the CNS characterized by complex and dynamic protein networks at both synaptic membranes. The cytomatrix at the active zone (CAZ) organizes the apparatus for the regulated release of transmitters from the presynapse. At the postsynaptic side, the postsynaptic density constitutes the machinery for detection, integration, and transduction of the transmitter signal. Both pre- and postsynaptic protein networks represent the molecular substrates for synaptic plasticity. Their function can be altered both by regulating their composition and by post-translational modification of their components. For a comprehensive understanding of synaptic networks the entire ensemble of synaptic proteins has to be considered. To support this, we established a comprehensive database for synaptic junction proteins (SynProt database) primarily based on proteomics data obtained from biochemical preparations of detergent-resistant synaptic junctions. The database currently contains 2,788 non-redundant entries of rat, mouse, and some human proteins, which mainly have been manually extracted from 12 proteomic studies and annotated for synaptic subcellular localization. Each dataset is completed with manually added information including protein classifiers as well as automatically retrieved and updated information from public databases (UniProt and PubMed). We intend that the database will be used to support modeling of synaptic protein networks and rational experimental design.

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          Most cited references89

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          The Universal Protein Resource (UniProt) in 2010

          The primary mission of UniProt is to support biological research by maintaining a stable, comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase, with extensive cross-references and querying interfaces freely accessible to the scientific community. UniProt is produced by the UniProt Consortium which consists of groups from the European Bioinformatics Institute (EBI), the Swiss Institute of Bioinformatics (SIB) and the Protein Information Resource (PIR). UniProt is comprised of four major components, each optimized for different uses: the UniProt Archive, the UniProt Knowledgebase, the UniProt Reference Clusters and the UniProt Metagenomic and Environmental Sequence Database. UniProt is updated and distributed every 3 weeks and can be accessed online for searches or download at http://www.uniprot.org.
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            Tripartite synapses: glia, the unacknowledged partner.

            According to the classical view of the nervous system, the numerically superior glial cells have inferior roles in that they provide an ideal environment for neuronal-cell function. However, there is a wave of new information suggesting that glia are intimately involved in the active control of neuronal activity and synaptic neurotransmission. Recent evidence shows that glia respond to neuronal activity with an elevation of their internal Ca2+ concentration, which triggers the release of chemical transmitters from glia themselves and, in turn, causes feedback regulation of neuronal activity and synaptic strength. In view of these new insights, this article suggests that perisynaptic Schwann cells and synaptically associated astrocytes should be viewed as integral modulatory elements of tripartite synapses.
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              Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin.

              NMDA receptors are linked to intracellular cytoskeletal and signaling molecules via the PSD-95 protein complex. We report a novel family of postsynaptic density (PSD) proteins, termed Shank, that binds via its PDZ domain to the C terminus of PSD-95-associated protein GKAP. A ternary complex of Shank/GKAP/PSD-95 assembles in heterologous cells and can be coimmunoprecipitated from rat brain. Synaptic localization of Shank in neurons is inhibited by a GKAP splice variant that lacks the Shank-binding C terminus. In addition to its PDZ domain, Shank contains a proline-rich region that binds to cortactin and a SAM domain that mediates multimerization. Shank may function as a scaffold protein in the PSD, potentially cross-linking NMDA receptor/PSD-95 complexes and coupling them to regulators of the actin cytoskeleton.
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                Author and article information

                Journal
                Front Synaptic Neurosci
                Front Synaptic Neurosci
                Front. Syn. Neurosci.
                Frontiers in Synaptic Neuroscience
                Frontiers Research Foundation
                1663-3563
                25 June 2012
                2012
                : 4
                : 1
                Affiliations
                [1] 1simpleDepartment of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology Magdeburg, Germany
                [2] 2simpleSpecial Lab Molecular Biology Techniques, Leibniz Institute for Neurobiology Magdeburg, Germany
                [3] 3simpleCenter for Behavioral Brain Science Magdeburg, Germany
                [4] 4simpleEmmy Noether Research Group Neuralomics, Leibniz Institute for Neurobiology Magdeburg, Germany
                [5] 5simpleInstitute for Pharmacology and Toxicology, Otto-von-Guericke University Magdeburg, Germany
                [6] 6simpleInstitute for Mathematical Optimization, Otto-von-Guericke University Magdeburg, Germany
                Author notes

                Edited by: Mary B. Kennedy, Caltech, USA

                Reviewed by: Mary B. Kennedy, Caltech, USA; Monica DiLuca, University of Milano, Italy

                *Correspondence: Daniela C. Dieterich, Institute for Pharmacology and Toxicology, Otto-von-Guericke University, Leipziger Strasse 44, D-39120 Magdeburg, Germany. e-mail: daniela.dieterich@ 123456med.ovgu.de

                Present address: Utz-Uwe Haus and Robert Weismantel, Institute for Operations Research, Swiss Federal Institute of Technology, Zurich, Switzerland.

                Rainer Pielot and Karl-Heinz Smalla have contributed equally to this work.

                Article
                10.3389/fnsyn.2012.00001
                3382120
                22737123
                60900429-496f-484d-978c-900478a6f354
                Copyright © 2012 Pielot, Smalla, Müller, Landgraf, Lehmann, Eisenschmidt, Haus, Weismantel, Gundelfinger and Dieterich.

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.

                History
                : 09 November 2011
                : 29 May 2012
                Page count
                Figures: 3, Tables: 4, Equations: 0, References: 106, Pages: 13, Words: 9730
                Categories
                Neuroscience
                Original Research

                Neurosciences
                synaptic junction,rat,proteomics,mouse,human,cytomatrix at the active zone,postsynaptic density,chemical synapse

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