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Tau mislocalization to dendritic spines and associated postsynaptic deficits are mediated through different and non-overlapping phosphorylation sites. Tau mislocalization to dendritic spines depends upon the phosphorylation of either Ser396 or Ser404 in the C-terminus. Postsynaptic dysfunction instead depends upon the phosphorylation of at least one of five residues in the proline-rich region of tau. The blockade of both glycogen synthetase kinase 3β and cyclin-dependent kinase 5 is required to prevent P301L-induced tau mislocalization to dendritic spines, supporting redundant pathways that control tau mislocalization to spines.
Pubmed ID: 31194886
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