Axonal Transport of Eukaryotic Translation Elongation Factor 1α mRNA Couples Transcription in the Nucleus to Long-Term Facilitation at the Synapse

Long-term synaptic plasticity requires both gene expression in the nucleus and local protein synthesis at synapses. The effector proteins that link molecular events in the cell body with local maintenance of synaptic strength are not known. We now show that treatment with serotonin (5-HT) that produ...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 100; no. 23; pp. 13680 - 13685
Main Authors Giustetto, Maurizio, Hegde, Ashok N., Si, Kausik, Casadio, Andrea, Inokuchi, Kaoru, Pei, Wanzheng, Kandel, Eric R., Schwartz, James H.
Format Journal Article
LanguageEnglish
Published National Academy of Sciences 11.11.2003
National Acad Sciences
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Summary:Long-term synaptic plasticity requires both gene expression in the nucleus and local protein synthesis at synapses. The effector proteins that link molecular events in the cell body with local maintenance of synaptic strength are not known. We now show that treatment with serotonin (5-HT) that produces long-term facilitation induces the Aplysia eukaryotic translation elongation factor 1α (Ap-eEF1A) as a late gene that might serve this coupling function in sensory neurons. Although the translation factor is induced, it is not transported into axon processes when the stimulation with 5-HT was restricted to the cell body. In contrast, its mRNA is transported when 5-HT was applied to both cell body and synapses. Intracellular injection of antisense oligonucleotides or antibodies that block the induction and expression of Ap-eEFIA do not affect the initial expression of long-term facilitation but do block its maintenance beyond 24 h. The transport of eEFIA protein and its mRNA to nerve terminals suggests that the translation factor plays a role in the local protein synthesis that is essential for maintaining newly formed synapses.
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Present address: Dipartimento di Anatomia, Farmacologia e Medicina Legale, Universita' degli Studi di Torino, 10126 Torino, Italy.
Present address: Mitsubishi-Kasei Institute of Life Sciences, Minami-Ooya, Machida-shi, Tokyo 194-8511, Japan.
Abbreviations: eEF1A, eukaryotic translation elongation factor 1α; Ap-eEFIA, Aplysia eEF1A; 5-HT, serotonin; EPSP, excitatory postsynaptic potential.
Present address: Department of Neurobiology and Anatomy, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157.
Contributed by Eric R. Kandel, September 4, 2003
Present address: Howard University Hospital, Washington, DC 20060.
M.G., A.N.H., and K.S. contributed equally to this work.
To whom correspondence should be addressed. E-mail: jhs6@columbia.edu.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1835674100