Figure 9. Trafficking pathways controlling localization of endosomal TLRs.
UNC93B1 interacts with several TLRs in the ER and facilitates loading into COPII vesicles. Unlike typical COPII loading factors, UNC93B1 remains associated with TLR9 and TLR7 after exit from the ER. Through its recruitment of AP-2, UNC93B1 is necessary for endocytosis of TLR9 from the plasma membrane into endosomes. TLR7 does not rely on this trafficking route. Instead, TLR7 utilizes AP-4 to bypass the cell surface and traffic directly to endosomes. This difference in trafficking may result in TLR9 and TLR7 accessing distinct compartments with unique functional properties related to the function of each receptor.