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PMID: 10777786 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 20 ·No. 9 ·2000-05-01 ·Pages 3214-20

Murphy DD, Rueter SM, Trojanowski JQ, Lee VM

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.

MeSH Terms
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
Chemicals
Nerve Tissue Proteins Oligonucleotides, Antisense Snca protein, rat Sncb protein, rat Synucleins alpha-Synuclein beta-Synuclein gamma-Synuclein
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Murphy D D
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104, USA.
Rueter S M
Trojanowski J Q
Lee V M
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2000-05-01
Pages
3214-20
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6773130
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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