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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Corradini, Eleonora Vallur, Raghavan Raaijmakers, Linsey M. Feil, Susanne Feil, Robert Heck, Albert J. R. Scholten, Arjen |
| Description | Author Affiliation: Corradini E ( From Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands); Vallur R ( ¶Interfakultäres Institut für Biochemie, Universität Tübingen, D-72074 Tübingen, Germany); Raaijmakers LM ( From Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands); Feil S ( ¶Interfakultäres Institut für Biochemie, Universität Tübingen, D-72074 Tübingen, Germany); Feil R ( ¶Interfakultäres Institut für Biochemie, Universität Tübingen, D-72074 Tübingen, Germany); Heck AJ ( From Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands); Scholten A ( From Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands) |
| Abstract | The cyclic nucleotide cyclic guanosine monophosphate (cGMP) plays an important role in learning and memory, but its signaling mechanisms in the mammalian brain are not fully understood. Using mass-spectrometry-based proteomics, we evaluated how the cerebellum adapts its (phospho)proteome in a knockout mouse model of cGMP-dependent protein kinase type I (cGKI). Our data reveal that a small subset of proteins in the cerebellum (â¼3% of the quantified proteins) became substantially differentially expressed in the absence of cGKI. More changes were observed at the phosphoproteome level, with hundreds of sites being differentially phosphorylated between wild-type and knockout cerebellum. Most of these phosphorylated sites do not represent known cGKI substrates. An integrative computational network analysis of the data indicated that the differentially expressed proteins and proteins harboring differentially phosphorylated sites largely belong to a tight network in the Purkinje cells of the cerebellum involving important cGMP/cAMP signaling nodes (e.g. PDE5 and PKARIIß) and Ca(2+) signaling (e.g. SERCA3). In this way, removal of cGKI could be linked to impaired cerebellar long-term depression at Purkinje cell synapses. In addition, we were able to identify a set of novel putative (phospho)proteins to be considered in this network. Overall, our data improve our understanding of cerebellar cGKI signaling and suggest novel players in cGKI-regulated synaptic plasticity. |
| File Format | HTM / HTML |
| ISSN | 15359476 |
| e-ISSN | 15359484 |
| DOI | 10.1074/mcp.M113.035154 |
| Journal | Molecular & Cellular Proteomics |
| Issue Number | 8 |
| Volume Number | 13 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 2014-08-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Proteomics Cerebellum Metabolism Cyclic Gmp-dependent Protein Kinase Type I Genetics Phosphoproteins Isolation & Purification Animals Cyclic Gmp Mice Mice, Knockout Phosphorylation Proteomics Signal Transduction Synapses Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Analytical Chemistry Molecular Biology Biochemistry |
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