Rapid Changes in Phospho-MAP/Tau Epitopes during Neuronal Stress: Cofilin-Actin Rods Primarily Recruit Microtubule Binding Domain Epitopes Changes in Phospho-MAP/Tau during Neuronal Stress
2011

Rapid Changes in Phospho-MAP/Tau Epitopes during Neuronal Stress

publication Evidence: moderate

Author Information

Author(s): Whiteman Ineka T., Minamide Laurie S., Goh De Lian, Bamburg James R., Goldsbury Claire

Primary Institution: The Brain and Mind Research Institute, University of Sydney, Sydney, Australia

Hypothesis

Inhibiting mitochondrial function influences the phosphorylation state and localization of tau protein.

Conclusion

Mitochondrial inhibition leads to specific and sustained detection of 12E8 epitopes indicative of MAP phosphorylation, while other phospho-tau epitopes undergo dephosphorylation.

Supporting Evidence

  • Mitochondrial dysfunction initiates formation of neuritic inclusions that co-localize with actin depolymerizing factor/cofilin-actin rods.
  • 12E8 is the only epitope predominantly recruited to AC rods generated under mitochondrial inhibition.
  • ATP reduction leads to dephosphorylation of most phospho-tau epitopes except for 12E8.

Takeaway

When neurons are stressed, a specific part of a protein called tau gets more active, while other parts become less active. This might help us understand how brain diseases like Alzheimer's start.

Methodology

Primary neuronal cultures from chick tecta were treated with a mitochondrial inhibitor and analyzed for changes in tau phosphorylation and distribution using Western blotting and immunolabeling.

Limitations

The study is based on a cell culture model and may not fully represent in vivo conditions.

Participant Demographics

Chick primary neurons were used in the study.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0020878

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