Department of Neuroscience, Institute of Psychiatry, King's College London, MRC Centre for Neurodegeneration Research, De Crespigny Park, London SE5 8AF, UK.
Biochem Soc Trans. 2010 Aug;38(4):1012-5. doi: 10.1042/BST0381012.
Tau is an abundant microtubule-associated protein which regulates the stability of the cytoskeleton. Tau binds microtubules directly through microtubule-binding domains in its C-terminus. However, tau is not only located in the cytosol of cells, but also associated with other intracellular domains, including the plasma membrane, suggesting that tau may have additional functions other than stabilizing the neuronal cytoskeleton. Localization of tau at the cell surface appears to be dependent on interactions of the N-terminal projection domain of tau. Furthermore, membrane-associated tau is dephosphorylated at serine/threonine residues, suggesting that the phosphorylation state of tau regulates its intracellular trafficking. Dephosphorylation of tau may increase the association of tau with trafficking proteins which target tau to the plasma membrane. Thus it is possible that the hyperphosphoryation of tau may contribute to the pathogenesis of Alzheimer's disease by promoting the formation of neurofibrillary tangles from cytosolic tau, and also by inhibiting additional tau functions through disruption of its targeting to the plasma membrane.
tau 是一种丰富的微管相关蛋白，可调节细胞骨架的稳定性。tau 通过其 C 端的微管结合结构域直接结合微管。然而，tau 不仅位于细胞的细胞质中，而且还与其他细胞内结构域（包括质膜）相关联，这表明 tau 可能具有除稳定神经元细胞骨架之外的其他功能。tau 在细胞表面的定位似乎依赖于 tau 的 N 端突出结构域的相互作用。此外，位于膜上的 tau 在丝氨酸/苏氨酸残基上发生去磷酸化，表明 tau 的磷酸化状态调节其细胞内运输。tau 的去磷酸化可能会增加 tau 与靶向质膜的运输蛋白的结合，从而使 tau 更容易被运输到质膜上。因此，tau 的过度磷酸化可能通过促进细胞质 tau 形成神经原纤维缠结，并通过破坏其靶向质膜来抑制 tau 的其他功能，从而导致阿尔茨海默病的发病机制。
