PubMed: 22833681

Title
Interaction of endogenous tau protein with synaptic proteins is regulated by N-methyl-D-aspartate receptor-dependent tau phosphorylation.
Journal
The Journal of biological chemistry
Volume
287
Issue
None
Pages
32040-53
Date
2012-09-14
Authors
Boehm J | Bourgeois C | Dudilot A | Lauzon M | Leclerc N | Mondragón-Rodríguez S | Trillaud-Doppia E

Evidence 307339aaa9

Acute treatment of rTg4510 mice with an O-GlcNAcase inhibitor transiently reduced tau phosphorylation at epitopes implicated in tau pathology. More importantly, long-term inhibitor treatment strongly increased tau O-GlcNAcylation, reduced the number of dystrophic neurons, and protected against the formation of pathological tau species without altering the phosphorylation of non-pathological tau.

Evidence cda0826916

Hence, LTD-inducing NMDA receptor activation leads to an increase in tau phosphorylation at sites PHF-1, AT180, as well as AT8 and to a reduction at AT100.

Evidence 366dcf5625

This result is supported by recent studies showing that the interaction between Fyn and tau is regulated through tau phosphorylation at the AT8 site, increasing tau-Fyn interaction by 42-fold after tau is phosphorylated or bearing a phosphomimetic mutation at the AT8 site (63). In our experiments, tau phosphorylation at AT8 is strongly up-regulated through the activation of NMDA receptors (Fig. 3), suggesting that NMDA receptor activation could massively enhance the interaction between tau and Fyn.

Evidence 8530a292d6

This indicates that O-GlcNAcylation prevents the aggregation of tau in a manner that does not affect its normal phosphorylation state.

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.