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November 20, 2025Neuroscience ResearchOpen Access

Graded regulation of microtubule-binding of Tau by the phosphorylation state of the proline-rich region in living neurons

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Authors

RNRinaho NakataTTTomohiro ToriiTMTomohiro Miyasaka

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Implication

Experiment reveals phosphorylation moderates microtubule-binding dynamics in neurons, suggesting new insights into Tau regulation.

Key Points

  • The aim is to understand how phosphorylation affects Tau's binding to microtubules in neurons.
  • Used fluorescence recovery after photobleaching (FRAP) on primary cultured rat hippocampal neurons.
  • Developed a dephosphorylation-mimetic Tau mutant by substituting phosphorylation sites with alanine residues.
  • Compared the microtubule-binding dynamics of the mutant to wild-type Tau in experiments and simulations.
  • Overall number of non-phosphorylated sites predominantly modulates Tau-microtubule affinity.
  • Phosphorylation patterns have lesser impact than previously thought on Tau binding dynamics.

Cite This Study

Nakata et al. (2025) studied this question.

synapsesocial.com/papers/6924f084c0ce034ddc35040dhttps://doi.org/10.1016/j.neures.2025.104987
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