Tau phosphorylation impedes functionality of protective tau envelopes
Abstract
Tau is an axonal microtubule-associated protein. Tau interaction with microtubules is regulated by phosphorylation. Hyperphosphorylation of tau is implicated in microtubule destabilization related to neurodegenerative disorders. However, how tau phosphorylation leads to microtubule destabilization is unknown. Recently, it was shown that tau molecules on microtubules cooperatively assemble into cohesive layers termed envelopes. Tau envelopes protect microtubules against degradation by microtubule-severing enzymes, suggesting a functional link between envelopes and microtubule stability. Here we show that tau phosphorylation has deleterious effects on the microtubule-protective function of tau envelopes. Using reconstitution and live-cell experiments, we found that tau phosphorylation destabilizes tau envelopes and decreases their integrity, leading to reduced microtubule protection against microtubule-severing enzymes. Our data suggest that a perturbation of microtubule homeostasis linked to tau hyperphosphorylation in neurodegeneration can be explained by the disassembly and impaired functionality of the tau envelopes
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BibTeX
@article{siahaan2026phosphorylation,
title = {{Tau phosphorylation impedes functionality of protective tau envelopes}},
author = {Valerie Siahaan and Romana Weissova and Adela Karhanova and Eva Lanska and María J Ruiz-Estrada and Barbora Pukajová and Vojtěch Dostál and Véronique Henriot and Carsten Janke and Lenka Libusová and Marcus Braun and Martin Balastik and Zdenek Lansky},
journal = {Nature Chemical Biology},
year = {2026},
month = sep,
doi = {10.1038/s41589-025-02122-9},
url = {https://hal.science/hal-05768535v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Tau phosphorylation impedes functionality of protective tau envelopes
AU - Valerie Siahaan
AU - Romana Weissova
AU - Adela Karhanova
AU - Eva Lanska
AU - María J Ruiz-Estrada
AU - Barbora Pukajová
AU - Vojtěch Dostál
AU - Véronique Henriot
AU - Carsten Janke
AU - Lenka Libusová
AU - Marcus Braun
AU - Martin Balastik
AU - Zdenek Lansky
PY - 2026
DA - 2026/09/29
JO - Nature Chemical Biology
DO - 10.1038/s41589-025-02122-9
UR - https://hal.science/hal-05768535v1
AB - Tau is an axonal microtubule-associated protein. Tau interaction with microtubules is regulated by phosphorylation. Hyperphosphorylation of tau is implicated in microtubule destabilization related to neurodegenerative disorders. However, how tau phosphorylation leads to microtubule destabilization is unknown. Recently, it was shown that tau molecules on microtubules cooperatively assemble into cohesive layers termed envelopes. Tau envelopes protect microtubules against degradation by microtubule-severing enzymes, suggesting a functional link between envelopes and microtubule stability. Here we show that tau phosphorylation has deleterious effects on the microtubule-protective function of tau envelopes. Using reconstitution and live-cell experiments, we found that tau phosphorylation destabilizes tau envelopes and decreases their integrity, leading to reduced microtubule protection against microtubule-severing enzymes. Our data suggest that a perturbation of microtubule homeostasis linked to tau hyperphosphorylation in neurodegeneration can be explained by the disassembly and impaired functionality of the tau envelopes
SN - 1552-4450
SN - 1552-4469
ER -