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PMID: 15976091 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Intravesicular localization and exocytosis of alpha-synuclein and its aggregates.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 25 ·No. 25 ·2005-06-22 ·Pages 6016-24

Lee HJ, Patel S, Lee SJ

Abstract

Alpha-synuclein (alpha-syn), particularly in its aggregated forms, is implicated in the pathogenesis of Parkinson's disease and other related neurological disorders. However, the normal biology of alpha-syn and how it relates to the aggregation of the protein are not clearly understood. Because of the lack of the signal sequence and its predominant localization in the cytosol, alpha-syn is generally considered exclusively an intracellular protein. Contrary to this assumption, here, we show that a small percentage of newly synthesized alpha-syn is rapidly secreted from cells via unconventional, endoplasmic reticulum/Golgi-independent exocytosis. Consistent with this finding, we also demonstrate that a portion of cellular alpha-syn is present in the lumen of vesicles. Importantly, the intravesicular alpha-syn is more prone to aggregation than the cytosolic protein, and aggregated forms of alpha-syn are also secreted from cells. Furthermore, secretion of both monomeric and aggregated alpha-syn is elevated in response to proteasomal and mitochondrial dysfunction, cellular defects that are associated with Parkinson's pathogenesis. Thus, intravesicular localization and secretion are part of normal life cycle of alpha-syn and might also contribute to pathological function of this protein.

MeSH Terms
Animals Cell Line Cerebral Cortex/physiology Culture Media, Conditioned Exocytosis/physiology Genetic Vectors Humans Microsomes/physiology Neurons/physiology Rats alpha-Synuclein/genetics,physiology
Chemicals
Culture Media, Conditioned alpha-Synuclein
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lee He-Jin
The Parkinson's Institute, Sunnyvale, California 94089, USA.
Patel Smita
Lee Seung-Jae
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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
DOI
10.1523/JNEUROSCI.0692-05.2005
Published
2005-06-22
Pages
6016-24
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6724798
Subset
IM
External Links
PubMed source DOI: 10.1523/JNEUROSCI.0692-05.2005 PMC Full Text View journal details
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