Localisation and trafficking of Toll-like receptors: an important mode of regulation

In recent years the importance of the localisation and trafficking of Toll-like receptors (TLRs) and their adaptors within the cell has become apparent. Localisation and trafficking of both cell surface and endosomal TLRs, alongside their adaptors, appears to play an important role not only in ligand recognition but also in the downregulation of signaling following ligand stimulation. Chaperones, such as gp96, PRAT4A and Unc93B1 play a role in TLR localisation. TLR4 cycles between the Golgi and the plasma membrane until engaged by LPS. The MyD88-dependent pathway is then initiated at the plasma membrane, followed by the movement of the TLR4 complex into the endosome where the MyD88-independent pathway is activated. Several proteins, including Triad3A and TAG appear to be involved in the movement of TLR4 to the lysosome for degradation.