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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
JSON

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.

a(HBP:"Thiamet G") directlyDecreases act(p(ECCODE:"3.2.1.169")) View Subject | View Object

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p(HGNC:MAPT, pmod(Ph, Ser, 202)) positiveCorrelation p(HGNC:MAPT, pmod(HBP:"O-GlcNAcylation")) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 396)) positiveCorrelation p(HGNC:MAPT, pmod(HBP:"O-GlcNAcylation")) View Subject | View Object

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act(p(ECCODE:"3.2.1.169")) increases p(MGI:Mapt, pmod(HBP:"O-GlcNAcylation")) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:"O-GlcNAcylation")) positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:"O-GlcNAcylation")) positiveCorrelation p(HGNC:MAPT, pmod(Ph, Thr, 205)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:"O-GlcNAcylation")) positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 262)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:"O-GlcNAcylation")) positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 356)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:"O-GlcNAcylation")) positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 262)) positiveCorrelation p(HGNC:MAPT, pmod(HBP:"O-GlcNAcylation")) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 356)) positiveCorrelation p(HGNC:MAPT, pmod(HBP:"O-GlcNAcylation")) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Thr, 205)) positiveCorrelation p(HGNC:MAPT, pmod(HBP:"O-GlcNAcylation")) View Subject | View Object

Appears in Networks:

Evidence cda0826916
JSON

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.

act(a(MESH:"Receptors, N-Methyl-D-Aspartate")) increases p(HBP:"Tau epitope, AT8") View Subject | View Object

Appears in Networks:
Annotations
Uberon
hippocampal formation

act(a(MESH:"Receptors, N-Methyl-D-Aspartate")) increases a(HBP:"Tau epitope, PHF1") View Subject | View Object

Appears in Networks:
Annotations
Uberon
hippocampal formation

act(a(MESH:"Receptors, N-Methyl-D-Aspartate")) increases a(HBP:"Tau epitope, AT180") View Subject | View Object

Appears in Networks:
Annotations
Uberon
hippocampal formation

act(a(MESH:"Receptors, N-Methyl-D-Aspartate")) decreases a(HBP:"Tau epitope, AT100") View Subject | View Object

Appears in Networks:
Annotations
Uberon
hippocampal formation

Evidence 366dcf5625
JSON

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.

p(HBP:"Tau epitope, AT8") increases complex(p(HGNC:FYN), p(MGI:Mapt)) View Subject | View Object

Appears in Networks:
Annotations
Uberon
hippocampal formation

Evidence 8530a292d6
JSON

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

p(HGNC:MAPT, pmod(HBP:"O-GlcNAcylation")) decreases a(HBP:"Tau aggregates") View Subject | View Object

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