ArticleCell death & disease2021
The HSP GRP94 interacts with macrophage intracellular complement C3 and impacts M2 profile during ER stress.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
- Magnesium-tannic acid nanomedicines reprogram pro-fibrotic macrophages for hepatic fibrosis treatment via restoring endoplasmic reticulum homeostasis.Journal of nanobiotechnology · 2026Article
- Heat shock protein Gp96 (Grp94) in malaria: functional insights at the host-parasite interface and therapeutic perspectives.Frontiers in cell and developmental biology · 2026Review
- ATM interaction with GRP94 modulates oncogenic receptor expression and signaling and microglial activation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The chaperone GRP94 interacts with the proprotein convertase furin and regulates TGF-beta maturation in human primary M2 macrophages.Cell death discovery · 2025Article
- PTMs as molecular encoders: reprogramming chaperones into epichaperomes for network control in disease.Trends in biochemical sciences · 2025Review
- Perfluorobutane-enhanced US Targeting M2 Tumor-associated Macrophages for Predicting Programmed Cell Death-1 Response in Hepatocellular Carcinoma.Radiology. Imaging cancer · 2025Article
- Glucose-regulated protein 94 (Grp94/gp96) in viral pathogenesis: Insights into its role and therapeutic potentials.European journal of medicinal chemistry · 2025Review
- Inside job: Roles of intracellular C3.The Journal of allergy and clinical immunology · 2025Review
- Conformationally Restricted Grp94-Selective Inhibitors.ACS omega · 2025Article
- Investigation of the site 2 pocket of Grp94 with KUNG65 benzamide derivatives.Bioorganic & medicinal chemistry letters · 2024Article
- The endoplasmic reticulum stress protein GRP94 modulates cathepsin L activity in M2 macrophages in conditions of obesity-associated inflammation and contributes to their pro-inflammatory profile.International journal of obesity (2005) · 2024Article
- Tracing genetic diversity captures the molecular basis of misfolding disease.Nature communications · 2024Article
- Review
- Article
- Structural and functional complexity of HSP90 in cellular homeostasis and disease.Nature reviews. Molecular cell biology · 2023Review
- Unraveling the Mechanism of Epichaperome Modulation by Zelavespib: Biochemical Insights on Target Occupancy and Extended Residence Time at the Site of Action.Biomedicines · 2023Article
- MIF is a critical regulator of mononuclear phagocytic infiltration in hepatocellular carcinoma.iScience · 2023Article
- How aberrant N-glycosylation can alter protein functionality and ligand binding: An atomistic view.Structure (London, England : 1993) · 2023Article
- New insight of complement system in the process of vascular calcification.Journal of cellular and molecular medicine · 2023Review
- The role of the complosome in health and disease.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of GRP94, an endoplasmic reticulum (ER) stress protein with both pro- and anti-inflammatory functions, has not been investigated in macrophages during ER stress, whereas ER stress has been reported in many diseases involving macrophages. In this work, we studied GRP94 in M1/LPS + IFNγ and M2/IL-4 primary macrophages derived from human monocytes (isolated from buffy coats), in basal and ER stress conditions induced by thapsigargin (Tg), an inducer of ER calcium depletion and tunicamycin (Tm), an inhibitor of N-glycosylation. We found that GRP94 was expressed on the membrane of M2 but not M1 macrophages. In M2, Tg, but not Tm, while decreased GRP94 content in the membrane, it induced its secretion. This correlated with the induction of a pro-inflammatory profile, which was dependent on the UPR IRE1α arm activation and on a functional GRP94. As we previously reported that GRP94 associated with complement C3 at the extracellular level, we analyzed C3 and confirmed GRP94-C3 interaction in our experimental model. Further, Tg increased this interaction and, in these conditions, C3b and cathepsin L were detected in the extracellular medium where GRP94 co-immunoprecipitated with C3 and C3b. Finally, we showed that the C3b inactivated fragment, iC3b, only present on non-stressed M2, depended on functional GRP94, making both GRP94 and iC3b potential markers of M2 cells. In conclusion, our results show that GRP94 is co-secreted with C3 under ER stress conditions which may facilitate its cleavage by cathepsin L, thus contributing to the pro-inflammatory profile observed in stressed M2 macrophages.
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