Annexins A2 and A6 interact with the extreme N terminus of tau and thereby contribute to tau's axonal localization [Neurobiology]

We report here that tau interacts with the Ca2+-regulated plasma membrane–binding protein annexin A2 (AnxA2) via tau's extreme N terminus encoded by the first exon (E1). Bioinformatics analysis identified two conserved eight-amino-acids-long motifs within E1 in mammals. Using a heterologous yeast system, we found that disease-related mutations and pseudophosphorylation of Tyr-18, located within E1 but outside of the two conserved regions, do not influence tau's interaction with AnxA2. We further observed that tau interacts with the core domain of AnxA2 in a Ca2+-induced open conformation and interacts also with AnxA6. Moreover, lack of E1 moderately increased tau's association rate to microtubules, consistent with the supposition that the presence of the tau–annexin interaction reduces the availability of tau to interact with microtubules. Of note, intracellular competition through overexpression of E1-containing constructs reduced tau's axonal enrichment in primary neurons. Our results suggest that the E1-mediated tau–annexin interaction contributes to the enrichment of tau in the axon and is involved in its redistribution in pathological conditions.

Source: Journal of Biological Chemistry - May 25, 2018 Category: Chemistry Authors: Anne Gauthier–Kemper, Maria Suarez Alonso, Frederik Sundermann, Benedikt Niewidok, Maria–Pilar Fernandez, Lidia Bakota, Jurgen Josef Heinisch, Roland Brandt Tags: Cell Biology Source Type: research