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Review
. 2014 Mar 18;15(3):4671-713.
doi: 10.3390/ijms15034671.

Tau protein modifications and interactions: their role in function and dysfunction

Anna Mietelska-Porowska  1 , Urszula Wasik  2 , Marcelina Goras  3 , Anna Filipek  4 , Grazyna Niewiadomska  5
Affiliations
Review

Tau protein modifications and interactions: their role in function and dysfunction

Anna Mietelska-Porowska et al. Int J Mol Sci. .

Abstract

Tau protein is abundant in the central nervous system and involved in microtubule assembly and stabilization. It is predominantly associated with axonal microtubules and present at lower level in dendrites where it is engaged in signaling functions. Post-translational modifications of tau and its interaction with several proteins play an important regulatory role in the physiology of tau. As a consequence of abnormal modifications and expression, tau is redistributed from neuronal processes to the soma and forms toxic oligomers or aggregated deposits. The accumulation of tau protein is increasingly recognized as the neuropathological hallmark of a number of dementia disorders known as tauopathies. Dysfunction of tau protein may contribute to collapse of cytoskeleton, thereby causing improper anterograde and retrograde movement of motor proteins and their cargos on microtubules. These disturbances in intraneuronal signaling may compromise synaptic transmission as well as trophic support mechanisms in neurons.

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Figures

Figure 1.
Figure 1.
Tau is a multi-functional protein. As a microtubule-associated protein tau contributes to microtubule dynamics and participates in neurite outgrowth, axonal transport and trophic signaling enhancement. Moreover, tau participates in cell signal transduction through the modulation of the activity of Src and Fyn kinases and PSD95 protein. In the nucleolar organizing region of cell, tau can also be involved in DNA repair and heat shock responses (left panel). Tau dysfunction leads to microtubule disintegration, tau filaments formation and intraneuronal signaling disorder and, as a consequence, to cell death (right panel).
Figure 2.
Figure 2.
Proposed sequence of stages leading to tau pathology. Detachment of tau from microtubules increases amount of misfolded tau monomers. Monomers aggregate into small soluble tau oligomers. Small soluble tau oligomers and tau monomers can proceed to form granular tau oligomers (GTOs). Probably both, small oligomers and GTOs form paired helical filaments (PHFs) but GTOs are considered to be the main precursors of PHFs. Subsequently PHFs spontaneously aggregate into neurofibrillary tangles (NFTs).
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