Abstract
Neurotransmitter release relies on an evolutionarily conserved presynaptic machinery. Nonetheless, some proteins occur in certain species and synapses, and are absent in others, indicating that they may have modulatory roles. How such proteins expand the power or versatility of the core release machinery is unclear. The presynaptic protein Mover/TPRGL/SVAP30 is heterogeneously expressed among synapses of the rodent brain, suggesting that it may add special functions to subtypes of presynaptic terminals. Mover is a synaptic vesicle-attached phosphoprotein that binds to Calmodulin and the active zone scaffolding protein Bassoon. Here we use a Mover knockout mouse line to investigate the role of Mover in the hippocampal mossy fiber (MF) to CA3 pyramidal cell synapse and Schaffer collateral to CA1. While Schaffer collateral synapses were unchanged by the knockout, the MFs showed strongly increased facilitation. The effect of Mover knockout in facilitation was both calcium- and age-dependent, having a stronger effect at higher calcium concentrations and in younger animals. Increasing cyclic adenosine monophosphate (cAMP) levels by forskolin equally potentiated both wildtype and knockout MF synapses, but occluded the increased facilitation observed in the knockout. These discoveries suggest that Mover has distinct roles at different synapses. At MF terminals, it acts to constrain the extent of presynaptic facilitation.
Highlights
The molecular machinery mediating neurotransmitter release is strongly conserved throughout evolution: Ca2+ triggers exocytosis of neurotransmitter from synaptic vesicles (SVs) in less than a millisecond by binding to Synaptotagmin, which together with Complexins activates a core fusion machinery composed of SNAREs and SV proteins (Südhof, 2013)
We found that the absence of Mover affects short-term plasticity in the hippocampal CA3 but not in CA1
We show that this effect is age- and Ca2+-dependent, and interacts with the cyclic adenosine monophosphate pathway in the mossy fiber (MF) synapses
Summary
The molecular machinery mediating neurotransmitter release is strongly conserved throughout evolution: Ca2+ triggers exocytosis of neurotransmitter from synaptic vesicles (SVs) in less than a millisecond by binding to Synaptotagmin, which together with Complexins activates a core fusion machinery composed of SNAREs and SV proteins (Südhof, 2013). These events are confined to specialized sites of the presynaptic plasma membrane, called active zones, by a network of proteins including RIMs, RIM binding proteins, Munc13s, α-liprins and CAST/ERC proteins. We show that this effect is age- and Ca2+-dependent, and interacts with the cyclic adenosine monophosphate (cAMP) pathway in the mossy fiber (MF) synapses
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