期刊
JOURNAL OF NEUROCHEMISTRY
卷 90, 期 6, 页码 1464-1476出版社
WILEY
DOI: 10.1111/j.1471-4159.2004.02634.x
关键词
Aplysia; eukaryotic elongation factor 2; rapamycin; S6 kinase; synaptic plasticity; translation
In Aplysia, serotonin mediates behavioral sensitization by increasing the strength of the synapse between sensory and motor neurons, a process known as facilitation. The retention of long-term facilitation is blocked by rapamycin, an inhibitor of a specific translational pathway. One possible rapamycin-sensitive target is the increased translation of 5'-terminal oligopyrimidine mRNAs. These transcripts encode components of the translational machinery and have been proposed to be important for retention of long-term facilitation. We have cloned the 5'-terminal oligopyrimidine mRNA encoding eukaryotic elongation factor 2 and shown that serotonin increased its translation in synaptosomes. Another possible rapamycin-sensitive target is the inactivation of eukaryotic elongation factor 2 kinase. Eukaryotic elongation factor 2 kinase phosphorylates and inactivates eukaryotic elongation factor 2, blocking translational elongation. Serotonin application decreased eukaryotic elongation factor 2 phosphorylation in synaptosomes and in isolated neurites, and this was blocked by rapamycin. We propose a role for the rapamycin-sensitive pathway in neurons. Stimulation blocks translation by inducing calcium entry and phosphorylation of eukaryotic elongation factor 2. This block is reversed through activation of the rapamycin-sensitive system and dephosphorylation of eukaryotic elongation factor 2.
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