Syk and Hrs Regulate TLR3-Mediated Antiviral Response in Murine Astrocytes

Figure 1

TLR3 signaling in astrocytes. Upon dsRNA recognition in the endosomal compartment, TLR3 undergoes dimerization and interacts with the TRIF adaptor molecule. TRIF activation is followed by TRAF6 and TRAF3 recruitment. TRAF6 conducts the signal via RIP-1 and RIP-3 kinases which facilitate NEMO, IKK-α, and IKK-β complex formation, followed by NF-κB phosphorylation and translocation into the nucleus. TRAF3 engages TBK1 and IKK-i/Ɛ for IRF3 and IRF7 activation, followed by their dimerization and translocation into the nucleus. This leads to the induction of type I IFNs and proinflammatory cytokine gene expression. The dotted arrows highlight possible roles of ESCRT-0 in TLR3 transport from the ER to the endosome, as well as the role of Hrs and Syk in TLR3 degradation.