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Review
. 2005 Jan;105(1):69-84.
doi: 10.1016/j.pharmthera.2004.10.012.

Modulation of neurotransmitter release by the second messenger-activated protein kinases: implications for presynaptic plasticity

A G Miriam Leenders  1 , Zu-Hang Sheng
Affiliations
Review

Modulation of neurotransmitter release by the second messenger-activated protein kinases: implications for presynaptic plasticity

A G Miriam Leenders et al. Pharmacol Ther. 2005 Jan.

Abstract

Activity-dependent modulation of synaptic function and structure is emerging as one of the key mechanisms underlying synaptic plasticity. Whereas over the past decade considerable progress has been made in identifying postsynaptic mechanisms for synaptic plasticity, the presynaptic mechanisms involved have remained largely elusive. Recent evidence implicates that second messenger regulation of the protein interactions in synaptic vesicle release machinery is one mechanism by which cellular events modulate synaptic transmission. Thus, identifying protein kinases and their targets in nerve terminals, particularly those functionally regulated by synaptic activity or intracellular [Ca2+], is critical to the elucidation of the molecular mechanisms underlying modulation of neurotransmitter release and presynaptic plasticity. The phosphorylation and dephosphorylation states of synaptic proteins that mediate vesicle exocytosis could regulate the biochemical pathways leading from synaptic vesicle docking to fusion. However, functional evaluation of the activity-dependent phosphorylation events for modulating presynaptic functions still represents a considerable challenge. Here, we present a brief overview of the data on the newly identified candidate targets of the second messenger-activated protein kinases in the presynaptic release machinery and discuss the potential impact of these phosphorylation events in synaptic strength and presynaptic plasticity.

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Figures

Fig. 1
Fig. 1
The presynaptic proteins are proposed to be involved in presynaptic plasticity via their phosphorylation (P) by various kinases, including Ca/calmodulin-dependent kinase (CaMK) II (green) and protein kinase C (PKC, gold) or cAMP-dependent protein kinase (PKA, red), or by modulation via phorbol ester (PE, purple). These signal transduction events contribute to modulation of different steps in the synaptic vesicle cycle.
See this image and copyright information in PMC

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