Filamentous recombinant human Tau activates primary astrocytes via an integrin receptor complex

Peng Wang and Yihong Ye ()
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Peng Wang: National Institutes of Health
Yihong Ye: National Institutes of Health

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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 αV/β1 receptor binds recombinant human Tau, mediating the entry of Tau fibrils in astrocytes. The binding of distinct Tau species to the astrocytic αV/β1 receptor differentially activate integrin signaling. Furthermore, Tau-mediated activation of integrin signaling results in NFκB 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.

Date: 2021
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DOI: 10.1038/s41467-020-20322-w

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