5-HT stimulates eEF2 dephosphorylation in a rapamycin-sensitive manner in Aplysia neurites.

Abstract:

: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.

journal_name

J Neurochem

authors

Carroll M,Warren O,Fan X,Sossin WS

doi

10.1111/j.1471-4159.2004.02634.x

keywords:

subject

Has Abstract

pub_date

2004-09-01 00:00:00

pages

1464-76

issue

6

eissn

0022-3042

issn

1471-4159

pii

JNC2634

journal_volume

90

pub_type

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