Clustering of Tau fibrils impairs the synaptic composition of {alpha}3-Na+/K+-ATPase and AMPA receptors

We report that fibrillar Tau forms clusters at the plasma membrane following lateral diffusion. We found that the fibrils interact with the Na+/K+-ATPase (NKA) and AMPA receptors. The consequence of the clustering is a reduction in the amount of α3-NKA and an increase in the amount of GluA2-AMPA receptor at synapses. Furthermore, fibrillar Tau destabilizes functional NKA complexes. Tau and α-synuclein aggregates often co-exist in patients’ brains. We now show evidences for cross-talk between these pathogenic aggregates with α-synuclein fibrils dramatically enhancing fibrillar Tau clustering and synaptic localization. Our results suggest that fibrillar α-synuclein and Tau cross-talk at the plasma membrane imbalance neuronal homeostasis.

Source: EMBO Journal - February 1, 2019 Category: Molecular Biology Authors: Shrivastava, A. N., Redeker, V., Pieri, L., Bousset, L., Renner, M., Madiona, K., Mailhes-Hamon, C., Coens, A., Buee, L., Hantraye, P., Triller, A., Melki, R. Tags: Neuroscience Articles Source Type: research