Functional Links Between Aβ Toxicity, Endocytic Trafficking, and Alzheimer's Disease Risk Factors in Yeast
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Lindquist_Functional links.pdf
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Author(s)
Shulman, J. M.
Parrado, A.
Lindhagen-Persson, M.
Reiman, E. M.
Evans, D. A.
Bennett, David A.
Olofsson, A.
De Jager, Philip L.
Tanzi, R. E.
Caldwell, Kim A.
Date Issued
October 2011
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Treusch, S., S. Hamamichi, J. L. Goodman, K. E. S. Matlack, C. Y. Chung, V. Baru, J. M. Shulman, et al. “Functional Links Between A Toxicity, Endocytic Trafficking, and Alzheimer s Disease Risk Factors in Yeast.” Science 334, no. 6060 (December 1, 2011): 1241-1245.
Version
Author's final manuscript
Abstract
Aβ (beta-amyloid peptide) is an important contributor to Alzheimer’s disease (AD). We modeled Aβ toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to Aβ was previously unknown. The factors identified in yeast modified Aβ toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast, Aβ impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between Aβ, endocytosis, and human AD risk factors can be ascertained with yeast as a model system.
Description
2011 December 2 Author's Manuscript
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1126/science.1213210
