Single‐molecule imaging reveals Tau trapping at nanometer‐sized dynamic hot spots near the plasma membrane that persists after microtubule perturbation and cholesterol depletion
The EMBO Journal. 2022-08-25; 41(19):
DOI: 10.15252/embj.2022111265
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Padmanabhan P(1), Kneynsberg A(1), Cruz E(1), Amor R(2), Sibarita JB(3), Götz J(1).
Author information:
(1)Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
(2)Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
(3)Université de Bordeaux, Interdisciplinary Institute for Neuroscience, UMR, Bordeaux, France.
Accumulation of aggregates of the microtubule-binding protein Tau is a
pathological hallmark of Alzheimer’s disease. While Tau is thought to primarily
associate with microtubules, it also interacts with and localizes to the plasma
membrane. However, little is known about how Tau behaves and organizes at the
plasma membrane of live cells. Using quantitative, single-molecule imaging, we
show that Tau exhibits spatial and kinetic heterogeneity near the plasma
membrane of live cells, resulting in the formation of nanometer-sized hot spots.
The hot spots lasted tens of seconds, much longer than the short dwell time
(∼ 40 ms) of Tau on microtubules. Pharmacological and biochemical disruption of
Tau/microtubule interactions did not prevent hot spot formation, suggesting that
these are different from the reported Tau condensation on microtubules. Although
cholesterol removal has been shown to reduce Tau pathology, its acute depletion
did not affect Tau hot spot dynamics. Our study identifies an intrinsic dynamic
property of Tau near the plasma membrane that may facilitate the formation of
assembly sites for Tau to assume its physiological and pathological functions.
© 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.