. Interaction of Endogenous Tau Protein with Synaptic Proteins Is Regulated by N-Methyl-D-aspartate Receptor-dependent Tau Phosphorylation. J Biol Chem. 2012 Sep 14;287(38):32040-53. PubMed.

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  1. Mondragon-Rodriguez and colleagues confirm a role for tau in the dendrite under physiological conditions and address the role that distinct phospho-epitopes of tau have in mediating Aβ toxicity, in responding to NMDA, and in interaction of tau with PSD95. The stepwise phosphorylation response of tau upon stimulation with NMDA is interesting. The authors also conclude that mutating specific Ser/Thr tau sites to Ala increases tau’s interaction with PSD95 to different degrees depending on the mutated site (AT180 mutant >AT8 mutant >AT100 mutant).

    It would be interesting to 1) use phosphomimetics (as under disease conditions, tau is massively phosphorylated), and 2) determine how the mutations affect phosphorylation of T1472 of the NR2B subunit of the glutamate receptor. The authors of the study suggest that by combining their data with those in the literature that PSD95, NMDAR, Fyn, and tau may form a complex in the postsynaptic density. In fact this is what we have suggested previously (see Fig. 1; Ittner and Götz, 2011), based on our work published a year earlier (Ittner et al., 2010).

    References:

    . Amyloid-β and tau--a toxic pas de deux in Alzheimer's disease. Nat Rev Neurosci. 2011 Feb;12(2):65-72. PubMed.

    . Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models. Cell. 2010 Aug 6;142(3):387-97. PubMed.