• FRET
• biosensor
• neurodegeneration
• Tau

Tau is a microtubule-associated protein mainly expressed in neurons, encoded by the MAPT gene. Mutations in the MAPT locus lead to abnormal accumulation of hyperphosporylated tau in abundant intracellular inclusions known as neurofibrillary tangles (NFTs), a common feature of a group of neurodegenerative diseases known as Tauopathies.
In order to characterize the effect of ΔK280 and Q336H MAPT mutations FRET and FRAP techniques have been employed.To this aim the Conformational-Sensitive Tau Sensor (CST) that is based on the full length tau isoform 4R0N with the ECFP fused at the N-terminus and the EYFP at the C-terminus have been used. Since the CST allows to evaluate the changing in protein conformation and tau interactions with microtubules in living cells,two mutated CST constructs have been generated.
The study has revealed that Q336H and ΔK280 induced conformational changes in tau protein.In particular, Q336H alters the conformation by allowing the two ends of Tau protein to approach each other in a more closed loop-like structure. On the contrary, ΔK280 determined a conformational change by inducing a more relaxed three-dimensional structure and altered Tau stability on Microtubules by increasing the soluble Tau protein.