Browsing by Author "Treusch, Sebastian"

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    Functional Links Between A beta Toxicity, Endocytic Trafficking, and Alzheimer's Disease Risk Factors in Yeast
    (American Association for the Advancement of Science, 2011) Treusch, Sebastian; Hamamichi, Shusei; Goodman, Jessica L.; Matlack, Kent E. S.; Chung, Chee Yeun; Baru, Valeriya; Shulman, Joshua M.; Parrado, Antonio; Bevis, Brooke J.; Valastyan, Julie S.; Han, Haesun; Lindhagen-Persson, Malin; Reiman, Eric M.; Evans, Denis A.; Bennett, David A.; Olofsson, Anders; DeJager, Philip L.; Tanzi, Rudolph E.; Caldwell, Kim A.; Caldwell, Guy A.; Lindquist, Susan; Massachusetts Institute of Technology (MIT); Whitehead Institute; Howard Hughes Medical Institute; University of Alabama Tuscaloosa; Harvard University; Brigham & Women's Hospital; Harvard Medical School; Broad Institute; Massachusetts General Hospital; Umea University; Translational Genomics Research Institute; University of Arizona; Banner Research; Banner Health; Banner Alzheimer's Institute; Rush University
    A beta (beta-amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled A beta 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 A beta was previously unknown. The factors identified in yeast modified A beta toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast, A beta impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between A beta, endocytosis, and human AD risk factors can be ascertained with yeast as a model system.