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Bimolecular Fluorescence Complementation; Lighting-Up Tau-Tau Interaction in Living Cells

2013; Public Library of Science; Volume: 8; Issue: 12 Linguagem: Inglês

10.1371/journal.pone.0081682

1932-6203

HyeJin Tak, Md. Mamunul Haque, Min Jung Kim, Joo Hyun Lee, Ja‐Hyun Baik, Young Soo Kim, Dong Jin Kim, Régis Grailhe, Yun Kyung Kim,

Molecular Sensors and Ion Detection

Abnormal tau aggregation is a pathological hallmark of many neurodegenerative disorders and it is becoming apparent that soluble tau aggregates play a key role in neurodegeneration and memory impairment. Despite this pathological importance, there is currently no single method that allows monitoring soluble tau species in living cells. In this regard, we developed a cell-based sensor that visualizes tau self-assembly. By introducing bimolecular fluorescence complementation (BiFC) technique to tau, we were able to achieve spatial and temporal resolution of tau-tau interactions in a range of states, from soluble dimers to large aggregates. Under basal conditions, tau-BiFC cells exhibited little fluorescence intensity, implying that the majority of tau molecules exist as monomers. Upon chemically induced tau hyperphosphorylation, BiFC fluorescence greatly increased, indicating an increased level of tau-tau interactions. As an indicator of tau assembly, our BiFC sensor would be a useful tool for investigating tau pathology.