Rapid, Activity-Induced Increase in Tissue Plasminogen Activator Is Mediated by Metabotropic Glutamate Receptor-Dependent mRNA Translation

• DOI: 10.1523/jneurosci.2457-04.2004
• Publication Date: 2004-10-20T23:09:17Z
• Authors: Chan Y. Shin; Mitchell Kundel; David G. Wells
• Keywords: Neurons; 0301 basic medicine; Neuronal Plasticity; Time Factors; Glutamic Acid; Polyadenylation; Receptors, Metabotropic Glutamate; Receptors, N-Methyl-D-Aspartate; Rats; 3. Good health; 03 medical and health sciences; Gene Expression Regulation; Protein Biosynthesis; Tissue Plasminogen Activator; Calcium-Calmodulin-Dependent Protein Kinases; Synapses; Animals; RNA, Messenger; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cells, Cultured; Synaptosomes

Long-term synaptic plasticity is both protein synthesis-dependent and synapse-specific. Therefore, the identity of newly synthesized proteins, their localization, mechanism regulation are critical to our understanding this process. Tissue plasminogen activator (tPA) a secreted protease required for some forms long-term plasticity. Here, we show tPA activity rapidly increased in hippocampal neurons after glutamate stimulation. This increase corresponds an synthesis that results from translational activation mRNA present at time Furthermore, encoding dendrites polyadenylated Both polyadenylation subsequent dependent on metabotropic receptor (mGluR) activation. A similar mGluR-dependent was detected stimulation fraction isolated hippocampus, suggesting occurring synaptodendritic region. Finally, demonstrate bound by mRNA-binding CPEB (cytoplasmic element binding protein-1), known regulate translation via polyadenylation. These indicate capable synthesizing region, mGluR induces specific mRNA, suggest model whereby immediate early gene precedes transcription.