14-3-3/Tau Interaction and Tau Amyloidogenesis

The major function of microtubule-associated protein tau is to promote microtubule assembly in the central nervous system. However, aggregation of abnormally phosphorylated tau is a hallmark of tauopathies. Although the molecular mechanisms of conformational transitions and assembling of tau molecules into amyloid fibril remain largely unknown, several factors have been shown to promote tau aggregation, including mutations, polyanions, phosphorylation, and interactions with other proteins. 14-3-3 proteins are a family of highly conserved, multifunctional proteins that are mainly expressed in the central nervous system. Being a scaffolding protein, 14-3-3 proteins interact with tau and regulate tau phosphorylation by bridging tau with various protein kinases. 14-3-3 proteins also directly regulate tau aggregation via specific and non-specific interactions with tau. In this review, we summarize recent advances in characterization of tau conformation and tau/14-3-3 interaction. We discuss the connection between 14-3-3 binding and tau aggregation with a special emphasis on the regulatory role of 14-3-3 on tau conformation.