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Updated: May 15, 2026

Detection of Neu1 Sialidase Activity in Regulating TOLL-like Receptor Activation
Published on: September 8, 2010
Phosphoinositide-mediated adaptor recruitment controls Toll-like receptor signaling
Jonathan C Kagan1, Ruslan Medzhitov
1Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Abstract:
Toll-like receptors (TLRs) play a critical role in the immune system as sensors of microbial infection. Signaling downstream from TLRs is initiated by the recruitment of adaptor proteins, including MyD88 and TIRAP. These adaptors play essential roles in TLR signaling, but the mechanism of their function is currently unknown. Here we demonstrate that TIRAP and MyD88 have distinct functions and describe a mechanism of recruitment of TIRAP and MyD88 to TLR4. We find that TIRAP contains a phosphatidylinositol 4,5-bisphosphate (PIP2) binding domain, which mediates TIRAP recruitment to the plasma membrane. TIRAP then functions to facilitate MyD88 delivery to activated TLR4 to initiate signal transduction. These results establish that phosphoinositide-mediated adaptor recruitment initiates a specific signal-transduction pathway.
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