The Chaperone UNC93B1 Regulates Toll-like Receptor Stability Independently of Endosomal TLR Transport

Immunity
Karin PelkaEicke Latz

Abstract

Unc-93 homolog B1 (UNC93B1) is a key regulator of nucleic acid (NA)-sensing Toll-like receptors (TLRs). Loss of NA-sensing TLR responses in UNC93B1-deficient patients facilitates Herpes simplex virus type 1 (HSV-1) encephalitis. UNC93B1 is thought to guide NA-sensing TLRs from the endoplasmic reticulum (ER) to their respective endosomal signaling compartments and to guide the flagellin receptor TLR5 to the cell surface, raising the question of how UNC93B1 mediates differential TLR trafficking. Here, we report that UNC93B1 regulates a step upstream of the differential TLR trafficking process. We discovered that UNC93B1 deficiency resulted in near-complete loss of TLR3 and TLR7 proteins in primary splenic mouse dendritic cells and macrophages, showing that UNC93B1 is critical for maintaining TLR expression. Notably, expression of an ER-retained UNC93B1 version was sufficient to stabilize TLRs and largely restore endosomal TLR trafficking and activity. These data are critical for an understanding of how UNC93B1 can regulate the function of a broad subset of TLRs.

Citations

Nov 16, 2018·Journal of Virology·Kendra A BusseyMelanie M Brinkmann
Mar 23, 2019·Journal of Leukocyte Biology·Laura MarongiuFrancesca Granucci
Feb 23, 2020·Journal of Cell Science·Mira TohmeBénédicte Manoury
Feb 6, 2020·Veterinary Sciences·Sabari Nath Neerukonda, Upendra Katneni
Apr 7, 2020·Innate Immunity·Laurent Zablocki-ThomasPhilippe Benaroch
Oct 2, 2020·Microbiology and Molecular Biology Reviews : MMBR·Huifang Zhu, Chunfu Zheng
Feb 1, 2019·Genes·Isabel FreundAlexander H Dalpke
Oct 1, 2019·Annual Review of Virology·Melissa Kane, Tatyana V Golovkina
Sep 10, 2020·Journal of Cardiovascular Pharmacology·Vanessa Dela JustinaR Clinton Webb
Jul 28, 2020·International Journal of Molecular Sciences·Kevin DanastasAnthony L Cunningham
Dec 19, 2020·Journal of Cellular and Molecular Medicine·Yazdan MokhtariDavood Bashash
Jan 5, 2021·The Journal of Clinical Investigation·Daxing GaoShen-Ying Zhang
Oct 17, 2020·Drug Discovery Today·Vijay K Singh, Thomas M Seed
Jan 13, 2021·Nature Structural & Molecular Biology·Hanako IshidaToshiyuki Shimizu
Oct 30, 2020·OncoTargets and Therapy·Lilit KarapetyanDiwakar Davar
Nov 17, 2020·Frontiers in Cellular and Infection Microbiology·Grasielle Pereira JannuzziKaren Spadari Ferreira
Feb 10, 2021·International Journal of Molecular Sciences·Shruthi ThadaSanne Burkert
Feb 16, 2021·Frontiers in Endocrinology·Christopher R Shepard
Feb 13, 2021·Protein Science : a Publication of the Protein Society·Jinta Asami, Toshiyuki Shimizu
Feb 19, 2021·Frontiers in Immunology·Matylda Barbara MielcarskaFelix Ngosa Toka
Feb 27, 2021·Frontiers in Immunology·Haruna OkudeTaro Kawai
Mar 14, 2020·Cell·Katherine A Fitzgerald, Jonathan C Kagan
Apr 16, 2021·Frontiers in Immunology·Mona MotwaniKatherine A Fitzgerald
Apr 11, 2021·European Journal of Immunology·Zhenliang HeJin Zhong
Jul 2, 2021·Journal of Immunology Research·Payam BehzadiTomasz M Karpiński
Jul 18, 2021·Nature Reviews. Immunology·Nicholas A LindGregory M Barton
Jul 16, 2020·Immunity·GuanQun Liu, Michaela U Gack
Jul 6, 2021·International Immunology·Kensuke MiyakeYusuke Murakami
Aug 21, 2021·Journal of Zhejiang University. Science. B·Yujuan ChenHuashan Yi

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