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

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.

Keywords: chemical synapse; cytomatrix at the active zone; human; mouse; postsynaptic density; proteomics; rat; synaptic junction.

Figure 1

Screenshot of a sample query. The user can choose between a simple search for a keyword in all fields or an extended search for one or more keywords in the specified fields. Here an extended search for a group of proteins is shown, which matches the following criteria: (1) classified as “Scaffolding and adaptor proteins” and (2) a molecular weight between 80,000 and 90,000 Da. The keywords are connected with a logical “AND” to accommodate detailed searches.

Figure 2

Screenshot after the extended search. The search retrieves 23 proteins matching the user-specified criteria. To prevent overloading of the browser, a maximum of 10 entries are shown on one page. Entries in green are derived from proteomic studies or manually added. Red entries are derived from UniProt due to homology. By clicking on the “Go!” Button, the user can choose the dataset of choice. The third and the ninth position show entries of the well-known postsynaptic protein PSD-95/SAP90 from different species.

Figure 3

Screenshot of the result screen after a search for “PSD-95.” The field “Proteomics-Paper” shows the proteomic studies, in which this protein was identified. In this case, it was found in 10 out of 12 studies. The field “Classification 1” denotes the manually assigned classification of PSD-95/SAP90. The field “Ultrastructural Localization” shows studies, in which the localization of this protein was verified by immunogold-staining. In addition, some of the proteins were manually assigned to categories, which denote the localization (see Table 4). All other data were retrieved from UniProt.