Cell and Developmental Biology Programme Zdenek Lansky

16/03/202612:00R_473.10_AULACell and Developmental Biology ProgrammeZdenek LanskyThe Institute of Biotechnology of the Czech Academy of SciencesATP regulates tau-microtubule interactionHost: Surrey, ThomasAbstract:
Neuronal microtubule-associated protein tau can protect the microtubule surface, maintaining microtubule stability. In neurodegenerative diseases termed tauopathies, tau forms cyto-toxic aggregates presumably as a consequence of tau delocalization from microtubules, accompanied by an increase in cytoplasm-localized tau and microtubule destabilization. The underlying mechanisms, however, remain unclear. Here, we show that decline of adenosine triphosphate (ATP), related to aging and neurodegeneration, leads to tau delocalization from microtubules and microtubule disintegration. Combining reconstitution experiments with molecular modeling, we show that ATP stabilizes tau molecules on the microtubule surface through electrostatic interactions. We propose that pathological decline of ATP can destabilize microtubule-tau interactions and lead to an increase of cytoplasmic tau, providing a plausible functional link between ATP homeostasis and tauopathies