Skip to main content

MAPT

Developmental stage

Shorter forms or low molecular weight tau (lMW-tau) are generally expressed at early development stages and longer forms or high molecular weight tau (hMW-tau) in the adult brain.

Domain

The tau/MAP repeat binds to tubulin. Type I isoforms contain 3 repeats while type II isoforms contain 4 repeats.

Function

Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity. The C-terminus binds axonal microtubules while the N-terminus binds neural plasma membrane components, suggesting that tau functions as a linker protein between both. Axonal polarity is predetermined by tau localization (in the neuronal cell) in the domain of the cell body defined by the centrosome. The short isoforms allow plasticity of the cytoskeleton whereas the longer isoforms may preferentially play a role in its stabilization.

Involvement in disease

May be involved in the pathogenesis of cytoplasmic inclusions (as Mallory bodies) in livers of mice chronically intoxicated with Griseofulvin or DDC (3,5-diethoxycarbonyl-2,4-dihydrocollidine), a model for human alcoholic hepatitis. Alteration of Tau (abnormal phosphorylation and cross-linking) could contribute to Mallory bodies formation and disturbance of microtubule function in alcoholic liver disease.

Post-translational modifications

Polyubiquitinated. Requires functional TRAF6 and may provoke SQSTM1-dependent degradation by the proteasome (By similarity).

Phosphorylation at various serine and threonine residues in S-P or T-P motifs by proline-directed protein kinases (PDPK1, CDK1, CDK5, GSK3, MAPK) (a few sites per protein in interphase, more in mitosis), and at serine residues in K-X-G-S motifs by MAP/microtubule affinity-regulating kinase (MARK1, MARK2, MARK3, MARK4), causing detachment from microtubules, and their disassembly (By similarity). Phosphorylated by PHK. Dephosphorylation at several serine and threonine residues by the serine/threonine phosphatase PPP5C. Phosphorylation at Ser-554 by BRSK1 and BRSK2 in neurons affects ability to bind microtubules and plays a role in neuron polarization. Phosphorylation at Ser-188 by SGK1 mediates microtubule depolymerization and neurite formation in hippocampal neurons (By similarity).

Tissue specificity

Expressed in neurons and at a lower level in the liver and kidney. Isoform PNS-tau is expressed in the peripheral nervous system while the others are expressed in the central nervous system.

Cellular localization

  • Cytoplasm
  • Cytosol
  • Cell membrane
  • Peripheral membrane protein
  • Cytoplasmic side
  • Cytoplasm
  • Cytoskeleton
  • Cell projection
  • Axon
  • Cell projection
  • Dendrite
  • Secreted
  • Mostly found in the axons of neurons, in the cytosol and in association with plasma membrane components. Can be secreted; the secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10; it results in protein translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) followed by vesicle entry and secretion.

Alternative names

  • Microtubule-associated protein tau
  • Neurofibrillary tangle protein
  • Paired helical filament-tau
  • PHF-tau
  • Tau
  • Mtapt
  • Mapt

Target type

Proteins

Primary research area

Neuroscience

Molecular weight

76243Da