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UNC93B1 mediates differential trafficking of endosomal TLRs

Lee, Bettina L, Moon, Joanne E, Shu, Jeffrey H, Yuan, Lin, Newman, Zachary R, Schekman, Randy, Barton, Gregory M·2013·eLife
DOI 10.7554/elife.00291PMC PMC3576711
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Abstract

UNC93B1, a multipass transmembrane protein required for TLR3, TLR7, TLR9, TLR11, TLR12, and TLR13 function, controls trafficking of TLRs from the endoplasmic reticulum (ER) to endolysosomes. The mechanisms by which UNC93B1 mediates these regulatory effects remain unclear. Here, we demonstrate that UNC93B1 enters the secretory pathway and directly controls the packaging of TLRs into COPII vesicles that bud from the ER. Unlike other COPII loading factors, UNC93B1 remains associated with the TLRs through post-Golgi sorting steps. Unexpectedly, these steps are different among endosomal TLRs. TLR9 requires UNC93B1-mediated recruitment of adaptor protein complex 2 (AP-2) for delivery to endolysosomes while TLR7, TLR11, TLR12, and TLR13 utilize alternative trafficking pathways. Thus, our study describes a mechanism for differential sorting of endosomal TLRs by UNC93B1, which may explain the distinct roles played by these receptors in certain autoimmune diseases.

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Metadata

Authors
Lee, B. L., Moon, J. E., Shu, J. H., Yuan, L., Newman, Z. R., Schekman, R., & Barton, G. M.
Affiliations
  • Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
  • Division of Cell and Developmental Biology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2013-02-19
Volume
2
ISSN
2050-084X
DOI
10.7554/elife.00291
PMC
PMC3576711
Cited by
281
References
3
Language
en
Licence
Funders
  • National Institutes of Health (AI072429, AI063302)
  • Lupus Research Institute
  • Burroughs Wellcome Fund
  • Weisenfeld Fellowship

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