| Autor: |
Hyun-Soo Je, Jianzheng Zhou, Feng Yang, Bai Lu |
| Předmět: |
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| Zdroj: |
Journal of Neuroscience; 12/14/2005, Vol. 25 Issue 50, p11719-11729, 11p, 8 Graphs |
| Abstrakt: |
Although neurotrophins elicit both acute and long-term effects, it is unclear whether the two modes of action are mediated by the same or different mechanisms. Using neuromuscular junction (NMJ) as a model system, we identified three characteristic features required for long-term, but not acute, forms of synaptic modulation by neurotrophin-3 (NT-3): endocytosis of NT-3-receptor complex, activation of the PI3 kinase substrate Akt, and new protein synthesis. Long-term effects were eliminated when NT-3 was conjugated to a bead that was too large to be endocytosed or when dominant-negative dynamin was expressed in presynaptic neurons. Presynaptic inhibition of Akt also selectively prevented NT-3-mediated long-term effects. Blockade of protein translation by the mammalian target of rapamycin inhibitor rapamycin prevented the long-term structural and functional changes at the NMJ, without affecting the acute potentiation of synaptic transmission by NT-3. These results reveal fundamental differences between acute and long-term modulation by neurotrophins. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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