Tau has canonically been considered as an axonal protein, but studies have observed tau localization in other subcellular domains of neurons. This relocated tau has been identified in both physiological and pathological conditions, and it is often labeled mislocalized. Furthermore, these forms of tau are referred to as “hyperphosphorylated” without specifying the phosphosites involved. On the contrary, we speculate that tau may have multiple physiological functions in various locations regulated via specific phosphorylation sites, although this picture is obscured by a lack of comprehensive phosphosite analysis. Here, we examine findings in the literature on the subcellular location of tau and potential roles tau has in those regions. We intentionally focus on the site-specific phosphorylated patterns involved in governing these properties, which are not well elucidated. To facilitate understanding of these events, we have begun establishing a comprehensive map of tau phosphorylation signatures. Such efforts may clarify tau’s diverse physiological functions beyond the axon as well as promote development of novel therapeutic strategies directed against distinct tau subpopulations.

Tau 通常被认为是一种轴突蛋白，但研究观察到 tau 定位于神经元的其他亚细胞域。这种重新定位的 tau 蛋白已在生理和病理条件下被识别，并且通常被标记为错误定位。此外，这些形式的 tau 蛋白被称为“过度磷酸化”，但未具体说明所涉及的磷酸位点。相反，我们推测 tau 蛋白可能在通过特定磷酸化位点调节的不同位置具有多种生理功能，尽管由于缺乏全面的磷酸化位点分析而使这一情况变得模糊。在这里，我们研究了文献中关于 tau 的亚细胞定位以及 tau 在这些区域中的潜在作用的发现。我们有意关注参与控制这些特性的位点特异性磷酸化模式，但目前尚未得到很好的阐明。为了促进对这些事件的理解，我们已经开始建立 tau 磷酸化特征的综合图谱。这些努力可能会阐明 tau 蛋白在轴突之外的多种生理功能，并促进针对不同 tau 蛋白亚群的新型治疗策略的开发。