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Review
. 2006 Jul 5;26(27):7147-50.
doi: 10.1523/JNEUROSCI.1797-06.2006.

Current advances in local protein synthesis and synaptic plasticity

Affiliations
Review

Current advances in local protein synthesis and synaptic plasticity

Brad E Pfeiffer et al. J Neurosci. .

Abstract

Local or dendritic protein synthesis is required for long-term functional synaptic change, such as long-term potentiation (LTP) and long-term depression (LTD). LTP and LTD both rely on similar signal transduction cascades, which regulate translation initiation. Current research indicates that the specificity by which new proteins participate in either LTP or LTD may be determined in part by specific RNA-binding proteins as well as activity-dependent capture.

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Figures

Figure 1.
Figure 1.
Convergence and divergence of mechanisms for protein synthesis-dependent LTP and LTD. Protein synthesis-dependent LTP (L-LTP) and mGluR-LTD activate and use similar, if not identical, pathways. To simplify, not all protein synthesis regulatory pathways are included, and second-messenger pathways upstream of ERK and PI3 kinase (PI3K) are omitted. Coactivation of NMDARs and dopamine D1/D5 receptors initiates the insertion of glutamate receptors to the synaptic surface and stimulates both ERK and PI3 kinase. Alternatively, agonists of mGluR1/5 receptors initiate the internalization of glutamate receptors but similarly activate the ERK and PI3 kinase pathways. L-LTP- and mGluR-LTD-inducing stimuli phosphorylate ERK, Mnk1, and eIF4E and stimulate eIF4F initiation complex assembly. Activated PI3 kinase phosphorylates mTOR, which in turn phosphorylates and inactivates the negative regulator of cap-dependent translation initiation, 4EBP, thereby enhancing translation initiation. Activated mTOR additionally phosphorylates and activates S6K (ribosomal S6 kinase), which leads to increased TOP (5′ terminal oligopyrimidine tract)-dependent translation. Proteins translated in response to synaptic activity may facilitate or maintain alterations in surface receptor number, synapse size, and/or synapse number. A few selected proteins, the synthesis of which have been demonstrated or are required for protein synthesis-dependent plasticity by the two different stimulation paradigms, are listed.

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