ArticleProceedings of the National Academy of Sciences of the United States of America2025
ER-resident CCDC134 safeguards TLR4 maturation by maintaining gp96 stability.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed.
- Expanding roles of N-glycosylation in the endoplasmic reticulum.Trends in cell biology · 2026Review
- Screening of serum biomarkers for coronary artery calcification using DIA quantitative proteomics and construction of a regression model.Frontiers in cardiovascular medicine · 2026Article
- ER-resident CCDC134 safeguards TLR4 maturation by maintaining gp96 stability.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Toll-like receptor 4 (TLR4), a pattern-recognition receptor located on the plasma membrane, senses extracellular danger signals to initiate inflammatory immune responses. It is initially synthesized in the endoplasmic reticulum (ER), undergoes N-linked glycosylation, and is subsequently transported to the Golgi before ultimately reaching the plasma membrane. However, the mechanisms underlying the processing and maturation of TLR4 in the ER remain elusive. Through whole genome-wide CRISPR screening, CCDC134 was identified as a critical and essential factor for TLR4-dependent inflammatory response. Localization of CCDC134 in the ER lumen rather than its exosome-mediated secretion is required for its role in TLR4 signaling. Loss of CCDC134 results in the retention of TLR4 in the ER for subsequent ER-associated degradation, and thus blockade of TLR4 maturation and plasma membrane trafficking. Defects in TLR4 processing and maturation in the ER in CCDC134-depleted cells are caused by aberrant hyperglycosylation and destabilization of glycoprotein 96 (gp96), a key chaperone of TLR4. These results suggest that CCDC134 controls gp96 glycosylation to facilitate TLR4 maturation in the ER.
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