[Seminar] “Physiology and pathology of neurons as deciphered from the dynamics of Tau” by Prof. Hiroko Bannai
Physiology and pathology of neurons as deciphered from the dynamics of Tau
Tauopathy is the neurological disorders caused by tau degeneration as exemplified by Alzheimer's disease. In such patients, tau proteins are denatured by excessive phosphorylation to form cytotoxic oligomers, which leads to the formation of pathological tau fiber formation. In vitro experiments have shown that tau is a protein capable of liquid-liquid phase separation (LLPS), and tau oligomerization and tau seed formation have been shown to occur in droplets of tau LLPS. However, the mechanism and timing of the formation of toxic tau oligomers and tau seeds in cells remain unclear. The difficulty in studying tau is that the time spent forming tau seeds and tau aggregates (decades in humans and months in model mice) is much longer than the time scales typically used for live cell imaging (milliseconds to days), and it is impossible to predict when and where tau oligomers and tau seeds are produced in the cell. Here, we present an optogenetic tool that can induce specific form of tau. Using the cells expressing this optogenetic tool, we showed that tau LLPS, aggresomes, and tau seeds were induced by irradiating them with light under various conditions. By using this optogenetic tool to induce tau oligomers and tau seeds in cells at targeted times, it will be possible to elucidate detailed process of tau aggregation in living cells, which was previously possible only in vitro.