Dopaminergic modulation of the hippocampal neuropil proteome identified by bioorthogonal noncanonical amino acid tagging (BONCAT) |
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Authors: | Hodas Jennifer J L Nehring Anne Höche Nicole Sweredoski Michael J Pielot Rainer Hess Sonja Tirrell David A Dieterich Daniela C Schuman Erin M |
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Institution: | Division of Biology, California Institute of Technology, Pasadena, CA, USA. |
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Abstract: | Local protein synthesis and its activity-dependent modulation via dopamine receptor stimulation play an important role in synaptic plasticity - allowing synapses to respond dynamically to changes in their activity patterns. We describe here the metabolic labeling, enrichment, and MS-based identification of candidate proteins specifically translated in intact hippocampal neuropil sections upon treatment with the selective D1/D5 receptor agonist SKF81297. Using the noncanonical amino acid azidohomoalanine and click chemistry, we identified over 300 newly synthesized proteins specific to dendrites and axons. Candidates specific for the SKF81297-treated samples were predominantly involved in protein synthesis and synapse-specific functions. Furthermore, we demonstrate a dendrite-specific increase in proteins synthesis upon application of SKF81297. This study provides the first snapshot in the dynamics of the dopaminergic hippocampal neuropil proteome. |
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