The Control of Neuronal Calcium Homeostasis by SNAP-25 and its Impact on Neurotransmitter Release.

ABSTRACT

The process of neurotransmitter release is central to the control of cell-to-cell communication in brain. SNAP-25 is a component of the SNARE complex, which, together with syntaxin-1 and synaptobrevin, mediates synaptic vesicle fusion with the plasma membrane. The genetic ablation of the protein or its proteolytic cleavage by botulinum neurotoxins results in a complete block of synaptic transmission. In the last years, several evidences have indicated that SNAP-25 also plays additional modulatory roles in neurotransmission through the control of voltage-gated calcium channels and presynaptic calcium ion concentration. Consistently, reduced levels of the protein affect presynaptic calcium homeostasis and result in pathologically enhanced glutamate exocytosis. The SNAP-25-dependent alterations of synaptic calcium dynamics may have direct impact on the development of neuropsychiatric disorders where the Snap-25 gene has been found to be involved.