Molecular Biology of the Cell track citations

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print January 2, 2008
Mol. Biol. Cell 10.1091/mbc.E07-08-0827

A more recent version of this article appeared on March 1, 2008 Originally published as MBC in Press, 10.1091/mbc.E07-08-0827 on January 9, 2008
This Article
Right arrow Full Text (PDF)
Right arrow Supplemental Materials
Right arrow All Versions of this Article:
E07-08-0827v1
E07-08-0827v2
19/3/1093    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Soper, J. H.
Right arrow Articles by Lee, V. M.-Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Soper, J. H.
Right arrow Articles by Lee, V. M.-Y.

Submitted on August 29, 2007
Revised on December 12, 2007
Accepted on December 20, 2007

{alpha}-Synuclein Induced Aggregation of Cytoplasmic Vesicles in Saccharomyces cerevisiae

James H. Soper,*{dagger} Subhojit Roy,*{dagger} Anna Stieber,*{dagger} Eliza Lee,*{dagger} Robert B. Wilson,{dagger} John Q. Trojanowski,*{dagger} Christopher G. Burd,{ddagger} and Virginia M.-Y. Lee*{dagger}

*Center for Neurodegenerative Disease Research, {dagger}Department of Pathology and Laboratory Medicine, {ddagger}Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104

Monitoring Editor: Jeffrey Brodsky

Aggregated {alpha}-synuclein ({alpha}-syn) fibrils form Lewy bodies (LBs), the signature lesions of Parkinson’s disease (PD) and related synucleinopathies, but the pathogenesis and neurodegenerative effects of LBs remain enigmatic. Recent studies have shown that when overexpressed in S. cerevisiae, {alpha}-syn localizes to plasma membranes and forms cytoplasmic accumulations similar to human {alpha}-syn inclusions. However, the exact nature, composition, temporal evolution and underlying mechanisms of yeast {alpha}-syn accumulations and their relevance to human synucleinopathies are unknown. Here we provide ultrastructural evidence that {alpha}-syn accumulations are not comprised of LB-like fibrils, but are associated with clusters of vesicles. Live-cell imaging showed {alpha}-syn initially localized to the plasma membrane, and subsequently formed accumulations in association with vesicles. Imaging of truncated and mutant forms of {alpha}-syn revealed the molecular determinants and vesicular trafficking pathways underlying this pathological process. Because vesicular clustering is also found in LB containing neurons of PD brains, {alpha}-syn mediated vesicular accumulation in yeast represents a model system to study specific aspects of neurodegeneration in PD and related synucleinopathies.

Address correspondence to: Virginia M.-Y. Lee (vmylee{at}mail.med.upenn.edu)






Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2008 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.