Microtubule-associated tau contributes to intra-dendritic trafficking of AMPA receptors in multiple ways

Abstract Microtubule-associated protein tau has crucial roles not only in the formation of some neurodegenerative disorders but also in normal synaptic functions, although its contributions to these are still unclear. Here, to reveal the influence of tau deletion on trafficking of synaptic receptors, we investigated the distribution of GluA2-containing AMPA-type glutamate receptors (AMPARs) within neuronal dendrites in wild-type and tau-deficient neurons using biochemical and laser-confocal imaging techniques. Under basal conditions, expression of GluA2 at tau-deficient synapses was almost normal; however, its level within dendrites in tau-deficient neurons was greater than that in wild-type neurons. After NMDA treatment, a decrease in GluA2-containing AMPARs at synapses was observed in wild-type neurons, but not in tau-deficient neurons. Single-cell imaging of GluA2 within dendrites demonstrated that wild-type neurons, but not tau-deficient neurons, showed enlargement of GluA2 puncta. Interestingly, we also found that NMDA rapidly reduced the number of GluA2 puncta without changing their size in tau-deficient neurons but not wild-type neurons. These results demonstrate the multiple contributions of tau to the maintenance of dynamic AMPAR trafficking within dendrites during both stimulated and unstimulated conditions.