Immunology

Regulating TLR Traffic Flow

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Science  22 Feb 2013:
Vol. 339, Issue 6122, pp. 885
DOI: 10.1126/science.339.6122.885-c

Sensing pathogen-derived nucleic acids is important for mounting antipathogen immunity. Such nucleic acid–sensing receptors are expressed intracellularly so that they do not inappropriately respond to self nucleic acids and cause autoimmunity. The specific mechanisms that regulate how these receptors, which include Toll-like receptors (TLRs) 3, 7, 8, and 9, reach their specific locations within cells, however, are not well understood. Lee et al. use cell biology techniques and mutational analysis to demonstrate that the transmembrane endoplasmic reticulum (ER) protein UNC93B1 is important for this process. UNC93B1 assists in the packaging of at least six TLRs in the ER and then remains associated with these receptors as they are processed through the Golgi apparatus. How TLRs go from the Golgi to their final destination, however, appears to be regulated by distinct mechanisms depending on the receptor. UNC93B1-dependent recruitment of AP-2 was required for TLR9 trafficking to endosomes; however, AP-2 was not required by other receptors. Thus, a variety of mechanisms may be employed to get TLRs from the Golgi to the right locations within the cell.

eLife 10.7554/eLife.00291 (2013).

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