ArticleNature communications2019
ZFYVE21 is a complement-induced Rab5 effector that activates non-canonical NF-κB via phosphoinosotide remodeling of endosomes.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 38 citations in OpenAlex.
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- Internalized Components of Membrane Attack Complexes Disrupt Proteostasis and Acquire Alarmin-Like Properties.bioRxiv : the preprint server for biology · 2026Article
- In vivo CRISPR/Cas9 screens identify new regulators of B cell activation and plasma cell differentiation.The Journal of experimental medicine · 2026Article
- Organelle stress in NLRP3 inflammasome: a central mediator of neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- Roles of endothelial cells during infection.Current opinion in immunology · 2025Review
- Engineering a Human-Sized Common Bile Duct Prototype with Regenerative Potential: In Vitro Evaluation of Mechanics, Function, Degradation, and Immune Modulation.Advanced healthcare materials · 2025Article
- Aging kidneys reveal underlying mechanisms of endothelial dysfunction.Kidney international · 2024Article
- ZFYVE21 promotes endothelial nitric oxide signaling and vascular barrier function in the kidney during aging.Kidney international · 2024Article
- Pten regulates endocytic trafficking of cell adhesion and Wnt signaling molecules to pattern the retina.Cell reports · 2024Article
- Distinct early role of PTEN regulation during HCMV infection of monocytes.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Appraisal of Chitosan-Coated Lipid Nano-Combination with Miltefosine and Albendazole in the Treatment of Murine Trichinellosis: Experimental Study with Evaluation of Immunological and Immunohistochemical Parameters.Acta parasitologica · 2024Article
- Hedgehog signalling in allograft vasculopathy: a new therapeutic target?Trends in pharmacological sciences · 2023Article
- A ZFYVE21-Rubicon-RNF34 signaling complex promotes endosome-associated inflammasome activity in endothelial cells.Nature communications · 2023Article
- Hedgehog-induced ZFYVE21 promotes chronic vascular inflammation by activating NLRP3 inflammasomes in T cells.Science signaling · 2023Article
- Protein-Coding Region Derived Small RNA in Exosomes from Influenza A Virus-Infected Cells.International journal of molecular sciences · 2023Article
- Membrane attack complexes, endothelial cell activation, and direct allorecognition.Frontiers in immunology · 2022Review
- The anti-parasitic drug miltefosine suppresses activation of human eosinophils and ameliorates allergic inflammation in mice.British journal of pharmacology · 2021Article
- How Structures of Complement Complexes Guide Therapeutic Design.Sub-cellular biochemistry · 2021Review
- Internalization of the Membrane Attack Complex Triggers NLRP3 Inflammasome Activation and IL-1β Secretion in Human Macrophages.Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
Abstract
Complement promotes vascular inflammation in transplant organ rejection and connective tissue diseases. Here we identify ZFYVE21 as a complement-induced Rab5 effector that induces non-canonical NF-κB in endothelial cells (EC). In response to membrane attack complexes (MAC), ZFYVE21 is post-translationally stabilized on MAC+Rab5+ endosomes in a Rab5- and PI(3)P-dependent manner. ZFYVE21 promotes SMURF2-mediated polyubiquitinylation and proteasome-dependent degradation of endosome-associated PTEN to induce vesicular enrichment of PI(3,4,5)P3 and sequential recruitment of activated Akt and NF-κB-inducing kinase (NIK). Pharmacologic alteration of cellular phosphoinositide content with miltefosine reduces ZFYVE21 induction, EC activation, and allograft vasculopathy in a humanized mouse model. ZFYVE21 induction distinctly occurs in response to MAC and is detected in human renal and synovial tissues. Our data identifies ZFYVE21 as a Rab5 effector, defines a Rab5-ZFYVE21-SMURF2-pAkt axis by which it mediates EC activation, and demonstrates a role for this pathway in complement-mediated conditions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.