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, has become the focus of research interest because alpha-synuclein has been increasingly implicated in the pathogenesis of Parkinson's and Alzheimer's disease. However, the normal functions of the synucleins are still unknown. For this reason, we characterized alpha-, beta-, and gamma-synuclein expression in primary hippocampal neuronal cultures and showed that the onset of alpha- and beta-synuclein expression was delayed after synaptic development, suggesting that these synucleins may not be essential for synapse formation. In mature cultured primary neurons, alpha- and beta-synuclein colocalized almost exclusively with synaptophysin in the presynaptic terminal, whereas little gamma-synuclein was expressed at all. To assess the function of alpha-synuclein, we suppressed expression of this protein with antisense oligonucleotide technology. Morphometric ultrastructural analysis of the alpha-synuclein 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 pools of synaptic vesicles in mature neurons.
Murphy
D D
DD
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104, USA.
Rueter
S M
SM
Trojanowski
J Q
JQ
Lee
V M
VM
D000818:Animals; D002478:Cells, Cultured; D006624:Hippocampus / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*; D051843:Synucleins; D051844:alpha-Synuclein; D051846:beta-Synuclein; D051845:gamma-Synuclein
D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; C497606:Snca protein, rat; C497609:Sncb protein, rat; D051843:Synucleins; D051844:alpha-Synuclein; D051846:beta-Synuclein; D051845:gamma-Synuclein