Presynaptic protein synthesis required for NT-3-induced long-term synaptic modulation

• Main Authors: Je H, Ji Yuanyuan, Wang Ying, Yang Feng, Wu Wei, Lu Bai
• Format: Article
• Language: English
• Published: BMC 2011-01-01
• Series: Molecular Brain
• Online Access: http://www.molecularbrain.com/content/4/1/1

<p>Abstract</p> <p>Background</p> <p>Neurotrophins elicit both acute and long-term modulation of synaptic transmission and plasticity. Previously, we demonstrated that the long-term synaptic modulation requires the endocytosis of neurotrophin-receptor complex, the activation of PI3K and Akt, and mTOR mediated protein synthesis. However, it is unclear whether the long-term synaptic modulation by neurotrophins depends on protein synthesis in pre- or post-synaptic cells.</p> <p>Results</p> <p>Here we have developed an inducible protein translation blocker, in which the kinase domain of protein kinase R (PKR) is fused with bacterial gyrase B domain (GyrB-PKR), which could be dimerized upon treatment with a cell permeable drug, coumermycin. By genetically targeting GyrB-PKR to specific cell types, we show that NT-3 induced long-term synaptic modulation requires presynaptic, but not postsynaptic protein synthesis.</p> <p>Conclusions</p> <p>Our results provide mechanistic insights into the cell-specific requirement for protein synthesis in the long-term synaptic modulation by neurotrophins. The GyrB-PKR system may be useful tool to study protein synthesis in a cell-specific manner.</p>