Tau proteins are proteins that perform the function of stabilizing microtubules. These proteins are abundant in nerve cells and are present to a much lesser degree in oligodendrocytes and astrocytes.
Tau proteins are mainly active in the distal portions of axons where they stabilize microtubules as well as providing flexibility.
The proteins work together with a globular protein called tubulin to stabilize microtubules and aid the assembly of tubulin in the mircrotubules.
Tau proteins achieve their control of microtubule stability through isoforms and phosphorylation.
Isoforms
Tau proteins exist as six different isoforms in brain tissue. These can be distinguished from each other based on their binding domains.
Three of the tau protein isoforms have three binding domains, while three of the proteins have four of these domains. The binding domains are found in the carboxy-terminus in the protein.
They are all positively-charged so they can bind to microtubules which have negative charge.
The tau proteins that have four binding domains are superior at stabilizing microtubules compared with the proteins that only have three binding domains.
The tau protein isoforms are produced through alternative splicing of a single gene called MAPT (microtubule-associated protein tau).
Phosphorylation
Phosphorylation of tau protein is mediated by several types of protein kinases such as the serine/threonine kinase PKN. Activated PKN phosphorylates tau, which disrupts the organization of microtubules.
Hyperphosphorylation of tau proteins can cause the helical and straight filaments to tangle (referred to as neurofibrillary tangles). These tangles contribute to the pathology of Alzheimer’s disease.
When a brain affected by Alzheimer’s disease is examined, all six isoforms of tau are often found hyperphosphorylated in paired helical filaments.
Deposits of abnormal aggregates enriched with tau isoforms have also been reported in some other neurodegenerative diseases.
Further Reading
Two genetic variants linked to Alzheimer's trigger microglial inflammation in females