ArticlePloS one2013
Rab6a/a' are important Golgi regulators of pro-inflammatory TNF secretion in macrophages.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 68 citations in OpenAlex.
- Disruption of macrophage pro-inflammatory cytokine release in Crohn's disease is associated with reduced optineurin expression in a subset of patients.Immunology · 2015Trial
- Organic manganese as a functional micronutrient: Promoting metabolic health and sustainable growth inAnimal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- Super-resolution microscopy reveals a Rab6a-dependent trafficking hub for rhodopsin at the mammalian rod photoreceptor Golgi.Biology open · 2025Article
- Super-resolution microscopy reveals a Rab6a-dependent trafficking hub for rhodopsin at the mammalian rod photoreceptor Golgi.bioRxiv : the preprint server for biology · 2025Article
- Naringenin: A Promising Immunomodulator for Anti-inflammatory, Neuroprotective and Anti-cancer Applications.Anti-inflammatory & anti-allergy agents in medicinal chemistry · 2025Review
- The Golgi Apparatus: A Key Player in Innate Immunity.International journal of molecular sciences · 2024Review
- Pro-inflammatory polarization and colorectal cancer modulate alternative and intronic polyadenylation in primary human macrophages.Frontiers in immunology · 2023Article
- Transcriptome analysis of PK-15 cells expressing CSFV NS4A.BMC veterinary research · 2022Article
- Micro-Players of Great Significance-Host microRNA Signature in Viral Infections in Humans and Animals.International journal of molecular sciences · 2022Review
- Regulated cell death (RCD) in cancer: key pathways and targeted therapies.Signal transduction and targeted therapy · 2022Review
- E3 ubiquitin ligase SYVN1 is a key positive regulator for GSDMD-mediated pyroptosis.Cell death & disease · 2022Article
- A Novel Drug Combination of Mangiferin and Cinnamic Acid Alleviates Rheumatoid Arthritis by Inhibiting TLR4/NFκB/NLRP3 Activation-Induced Pyroptosis.Frontiers in immunology · 2022Article
- A Brucella effector modulates the Arf6-Rab8a GTPase cascade to promote intravacuolar replication.The EMBO journal · 2021Article
- How cytosolic compartments play safeguard functions against neuroinflammation and cell death in cerebral ischemia.Metabolic brain disease · 2021Review
- Changes in proteins related to early nerve repair in a rat model of sciatic nerve injury.Neural regeneration research · 2021Article
- Review
- The Role of Mitophagy in Regulating Cell Death.Oxidative medicine and cellular longevity · 2021Review
- Wild-type huntingtin regulates human macrophage function.Scientific reports · 2020Article
- RAB6 GTPase regulates mammary secretory function by controlling the activation of STAT5.Development (Cambridge, England) · 2020Article
- PPT1 inhibition enhances the antitumor activity of anti-PD-1 antibody in melanoma.JCI insight · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Lipopolysaccharide (LPS)-activated macrophages secrete pro-inflammatory cytokines, including tumor necrosis factor (TNF) to elicit innate immune responses. Secretion of these cytokines is also a major contributing factor in chronic inflammatory disease. In previous studies we have begun to elucidate the pathways and molecules that mediate the intracellular trafficking and secretion of TNF. Rab6a and Rab6a' (collectively Rab6) are trans-Golgi-localized GTPases known for roles in maintaining Golgi structure and Golgi-associated trafficking. We found that induction of TNF secretion by LPS promoted the selective increase of Rab6 expression. Depletion of Rab6 (via siRNA and shRNA) resulted in reorganization of the Golgi ribbon into more compact structures that at the resolution of electron microcopy consisted of elongated Golgi stacks that likely arose from fusion of smaller Golgi elements. Concomitantly, the delivery of TNF to the cell surface and subsequent release into the media was reduced. Dominant negative mutants of Rab6 had similar effects in disrupting TNF secretion. In live cells, Rab6-GFP were localized on trans-Golgi network (TGN)-derived tubular carriers demarked by the golgin p230. Rab6 depletion and inactive mutants altered carrier egress and partially reduced p230 membrane association. Our results show that Rab6 acts on TNF trafficking at the level of TGN exit in tubular carriers and our findings suggest Rab6 may stabilize p230 on the tubules to facilitate TNF transport. Both Rab6 isoforms are needed in macrophages for Golgi stack organization and for the efficient post-Golgi transport of TNF. This work provides new insights into Rab6 function and into the role of the Golgi complex in cytokine secretion in inflammatory macrophages.
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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.