Tau

Tau is a protein that in humans is encoded by the MAPT (microtubule-associated protein tau) gene. It is abundant in the neurons of the central nervous system and is less common elsewhere, but is also expressed at very low levels in CNS astrocytes and oligodendrocytes.

Function

Tau proteins interact with tubulin to stabilize microtubules and promote tubulin assembly into microtubules. Tau has two ways of controlling microtubule stability: isoforms and phosphorylation.

Isoforms

Six tau isoforms exist in brain tissue. These result from alternative splicing in exons 2, 3, and 10 of the tau gene. They can be divided into two groups based on their number of binding domains. Three isoforms have three binding domains and the other three have four binding domains. The binding domains are located in the carboxy-terminus of the protein and bind to microtubules. The isoforms with four binding domains are better at stabilizing microtubules than those with three binding domains. The isoforms are differentially expressed in different cells and at different times in development.

Phosphorylation

Phosphorylation of tau is regulated by a host of kinases. For example, PKN, a protein kinase, phosphorylates tau, causing detachment from microtubules and disruption of the cytoskeleton. Hyperphosphorylation of the tau protein (tau inclusions, pTau) can result in the self-assembly of tangles of paired helical filaments and straight filaments, which are involved in the pathogenesis of Alzheimer's disease and other tauopathies.

Clinical significance

Tau protein is a highly soluble microtubule-associated protein (MAP). In humans, these proteins are mostly found in neurons compared to non-neuronal cells. One of tau's main functions is to modulate the stability of axonal microtubules. Other nervous system MAPs may perform similar functions, as suggested by tau knockout mice that did not show abnormalities in brain development – possibly due to compensation by other MAPs.

See also

• Alzheimer's disease
• Frontotemporal dementia and parkinsonism linked to chromosome 17
• Pick's disease
• Progressive supranuclear palsy
• Corticobasal degeneration
• Chronic traumatic encephalopathy

References

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