Mar 20, 2014

Visualizing the microtubule-associated protein tau in the nucleus

Science China. Life Sciences
Jing LuJürgen Götz

Abstract

Although tau is mainly known as an axonal microtubule-associated protein, many studies indicate that it is not restricted to this subcellular compartment. Assessing tau's subcellular distribution, however, is not trivial as is evident from transgenic mouse studies. When human tau is over-expressed, it can be immunohistochemically localized to axons and the somatodendritic domain, modeling what is found in neurodegenerative diseases such as Alzheimer's disease. Yet, in wild-type mice, despite its abundance, tau is difficult to visualize even in the axon. It is even more challenging to detect this protein in the nucleus, where tau has been proposed to protect DNA from damage. To establish a framework for future studies into tau's nuclear functions, we compared several methods to visualize endogenous nuclear tau in cell lines and mouse brain. While depending on the fixation and permeabilization protocol, we were able to detect nuclear tau in SH-SY5Y human neuroblastoma cells, we failed to do so in N2a murine neuroblastoma cells. As a second method we used subcellular fractionation of mouse tissue and found that in the nucleus tau is mainly present in a hypophosphorylated form. When either full-length or truncated human tau was exp...Continue Reading

  • References35
  • Citations16

References

  • References35
  • Citations16

Mentioned in this Paper

Familial Alzheimer Disease (FAD)
Microtubule-Associated Proteins
Central Neuroblastoma
Microtubule-Associated Protein 3
Murine
Protoplasm
Sample Fixation
MAPT protein, human
Alzheimer's Disease
Cell Nucleus

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