Abstract
Neurodegenerative diseases are devastating and incurable diseases that show a strong correlation to aging, posing great threats to both the population and the economy of the countries with a rapidly aging population such as the U.S. The human tau gene has been linked to a variety of neurodegenerative diseases including Alzheimer’s disease, whose role in the pathology still remains unclear. Although tau has been known as a microtubule binding protein, previous studies suggested that tau pathology may be attributed to other unknown cellular pathways. A yeast model for tauopathies established in this lab showed that expression of wild-type human tau in yeast can rescue the growth defect phenotype induced by tunicamycin, an ER stressor, and that disease related tau mutations impede such function in a severity correlated manner. Using this yeast model for tauopathies, I investigated the potential pathway involved in human tau pathology in Alzheimer’s disease utilizing complementation gene screening. Four genes that are either known tau interacting proteins or microtubule interacting proteins (BIM1, BIN1, RVS164, and STU2) were co-expressed with tau. Furthermore, fluorescence microscopy was utilized to test whether tau pathology was associated with changes in cellular localization and aggregation. Fluorescence microscopy was also used to test if Bin1 facilitates tau function through a direct physical interaction in yeast. Bin1 expression was observed to be beneficial for the rescue ability of tau and tau mutants, indicating the involvement of Bin1 in a tau pathological pathway and confirming the involvement of the unfolded protein response in tau pathology. Fluorescence microscopy studies showed no obvious change in localization and aggregation of Tau but revealed that Bin1 might enhance the function of tau variants by direct physical interactions under the ER stress induced by tunicamycin.