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

Abstract
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.
AuthorsD D Murphy, S M Rueter, J Q Trojanowski, V M Lee
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 20 Issue 9 Pg. 3214-20 (May 01 2000) ISSN: 1529-2401 [Electronic] United States
PMID10777786 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Nerve Tissue Proteins
  • Oligonucleotides, Antisense
  • Snca protein, rat
  • Sncb protein, rat
  • Synucleins
  • alpha-Synuclein
  • beta-Synuclein
  • gamma-Synuclein
Topics
  • Animals
  • Cells, Cultured
  • Hippocampus (drug effects, embryology, metabolism)
  • Nerve Tissue Proteins (drug effects, metabolism)
  • Neurodegenerative Diseases (metabolism)
  • Oligonucleotides, Antisense (pharmacology)
  • Presynaptic Terminals (drug effects, metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Synaptic Vesicles (drug effects, metabolism)
  • Synucleins
  • alpha-Synuclein
  • beta-Synuclein
  • gamma-Synuclein

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