Synucleins are developmentally expressed, and alpha-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons

alpha-, beta-, and gamma-Synuclein, a novel family of neuronal proteins, ha s become the focus of research interest because alpha-synuclein has been in creasingly implicated in the pathogenesis of Parkinson's and Alzheimer's di sease. However, the normal functions of the synucleins are still unknown. F or this reason, we characterized alpha-, beta-, and gamma-synuclein express ion in primary hippocampal neuronal cultures and showed that the onset of a lpha- and beta-synuclein expression was delayed after synaptic development, suggesting that these synucleins may not be essential for synapse formatio n. In mature cultured primary neurons, alpha- and beta-synuclein colocalize d almost exclusively with synaptophysin in the presynaptic terminal, wherea s little beta-synuclein was expressed at all. To assess the function of alp ha-synuclein, we suppressed expression of this protein with antisense oligo nucleotide technology. Morphometric ultrastructural analysis of the alpha-s ynuclein antisense oligonucleotide-treated cultures revealed a significant reduction in the distal pool of synaptic vesicles. These data suggest that one function of alpha-synuclein may be to regulate the size of distinct poo ls of synaptic vesicles in mature neurons.