| First Author | Wang P | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 95 |
| PubMed ID | 33398028 | Mgi Jnum | J:300955 |
| Mgi Id | MGI:6504670 | Doi | 10.1038/s41467-020-20322-w |
| Citation | Wang P, et al. (2021) Filamentous recombinant human Tau activates primary astrocytes via an integrin receptor complex. Nat Commun 12(1):95 |
| abstractText | 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 alphaV/beta1 receptor binds recombinant human Tau, mediating the entry of Tau fibrils in astrocytes. The binding of distinct Tau species to the astrocytic alphaV/beta1 receptor differentially activate integrin signaling. Furthermore, Tau-mediated activation of integrin signaling results in NFkappaB 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. |
