INVESTIGATING TAU DIMERIZATION: THE IMPLICATIONS OF TAU OLIGOMERS IN NEURODEGENERATION
Kevin Dervishi, Sarah Benbow, Stuart Feinstein.
University of California, Santa Barbara, Santa Barbara, CA.
Although it is well established that tau, a protein expressed almost exclusively in the nervous system, is essential for neuronal development and maintenance, our mechanistic understanding of tau action remains limited. Furthermore, tau dysfunction and misregulation correlate with Alzheimer’s disease and are also genetically linked to several related neurodegenerative dementias including FTDP-17, PSP, and Pick’s disease. Previous work has demonstrated that the C-terminal half of tau binds to microtubules, but the role of the N-terminal region remains enigmatic. Recent in vitro evidence strongly suggests that the N-terminal region of tau can form dimers as part of normal tau action. If tau dimerization is a relevant in vivo mechanism, it would provide important mechanistic insights into several key features of normal tau action. It may also be relevant to pathological tau action. Here, we seek to take the next important step forward by asking if tau dimerization occurs in living cells. By creating fluorescently tagged tau proteins, we will utilize FRET technology to test the hypothesis that tau can form dimers in cells, mediated by its N-terminal region. Presently, the necessary tau-FRET constructs are being built and cell culture procedures optimized. The goal of this study is to contribute to our understanding of both normal and pathological tau action.