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bioRxiv · 10.1101/2020.05.07.083295

An integrin receptor complex mediates filamentous Tau-induced activation of primary astrocytes

Ye, Y.·Wang, P.
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Abstract

Microtubule-associated protein Tau can form protein aggregates transmissible within the brain, correlating with the progression of tauopathies in humans. The transmission of aggregates requires neuron-released Tau to interact with surface receptors on target cells. However, the underlying molecular mechanisms in astrocytes and downstream effects are unclear. Here, using a spatially resolved proteomic mapping strategy, we show that integrin V/{beta}1 receptor binds recombinant human Tau, mediating the entry of Tau fibrils in astrocytes. The binding of distinct Tau species to the astrocytic V/{beta}1 receptor differentially activate integrin signaling. Furthermore, Tau-mediated activation of integrin signaling results in NF{kappa}B activation, causing upregulation of pro-inflammatory cytokines and chemokines, induction of a sub-group of neurotoxic astrocytic markers, and release of neurotoxic factors. Our findings suggest that filamentous recombinant human Tau-mediated activation of integrin signaling induces astrocyte conversion towards a neurotoxic state, providing a mechanistic insight into tauopathies.

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Ye, Y., Wang, P.. 2020-05-10. An integrin receptor complex mediates filamentous Tau-induced activation of primary astrocytes. https://doi.org/10.1101/2020.05.07.083295

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