Filamentous recombinant human Tau activates primary astrocytes via an integrin receptor complex.
IF: 17.694
Cited by: 32


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.


Spatial Proteomics

MeSH terms

Cells, Cultured
Focal Adhesion Protein-Tyrosine Kinases
HEK293 Cells
Heparan Sulfate Proteoglycans
Mice, Inbred C57BL
NF-kappa B
Protein Binding
Receptors, Vitronectin
Recombinant Proteins
STAT3 Transcription Factor
Signal Transduction
tau Proteins


Wang, Peng
Ye, Yihong

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