ArticleBlood advances2021
GDP/GTP exchange factor MADD drives activation and recruitment of secretory Rab GTPases to Weibel-Palade bodies.
Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- Seventh Åland Island Meeting on von Willebrand Disease.Haemophilia : the official journal of the World Federation of Hemophilia · 2026Article
- IG20/MADD gene functional isoform KIAA0358 can promote insulin secretion in glucose and repaglinide-induced pancreatic β-cells.Acta pharmacologica Sinica · 2026Article
- RAB5A regulates cell proliferation and lipid metabolism by modulating mitochondrial ROS via AMPK signaling pathway in ovarian granulosa cells.Redox biology · 2026Article
- MZF1-AS1/NSUN2 promotes the peritoneal metastasis of gastric cancer by enhancing the stability of RAB13 mRNA.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Article
- CRISPR/Cas9-mediated deletion of MADD induces cell cycle arrest and apoptosis in anaplastic thyroid cancer cells.Scientific reports · 2025Article
- Article
- The Rab3 family proteins in age-related neurodegeneration: unraveling molecular pathways and potential therapeutic targets.npj aging · 2025Review
- Rab3B Proteins: Cellular Functions, Regulatory Mechanisms, and Potential as a Cancer Therapy Target.Cell biochemistry and biophysics · 2025Review
- Weibel-Palade bodies - secretory organelles at the interface of inflammation and hemostasis.Frontiers in cell and developmental biology · 2025Review
- The proteomic landscape of in vitro cultured endothelial cells across vascular beds.Communications biology · 2024Article
- RAB3 phosphorylation by pathogenic LRRK2 impairs trafficking of synaptic vesicle precursors.The Journal of cell biology · 2024Article
- A splice site variant in MADD affects hormone expression in pancreatic β cells and pituitary gonadotropes.JCI insight · 2024Article
- MADD regulates natural killer cell degranulation through Rab27a activation.Journal of cell science · 2024Article
- RAB3 phosphorylation by pathogenic LRRK2 impairs trafficking of synaptic vesicle precursors.bioRxiv : the preprint server for biology · 2023Article
- MAP kinase activating death domain deficiency is a novel cause of impaired lymphocyte cytotoxicity.Blood advances · 2023Article
- Mutations in Neurobeachin-like 2 do not impact Weibel-Palade body biogenesis and von Willebrand factor secretion in gray platelet syndrome Endothelial Colony Forming Cells.Research and practice in thrombosis and haemostasis · 2023Article
- [miR-125b-5p inhibits proliferation and migration of osteosarcoma cells by negatively regulating RAB3D expression].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Automated segmentation and quantitative analysis of organelle morphology, localization and content using CellProfiler.PloS one · 2023Article
- Dispatch and delivery at the ER-Golgi interface: how endothelial cells tune their hemostatic response.The FEBS journal · 2022Article
- Rab GTPases as Modulators of Vascular Function.Cells · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
von Willebrand factor (VWF) is an essential hemostatic protein that is synthesized and secreted by endothelial cells and stored in Weibel-Palade bodies (WPBs). The secretory Rab GTPases Rab27A, Rab3B, and Rab3D have been linked with WPB trafficking and secretion. How these Rabs are activated and recruited to WPBs remains elusive. In this study, we identified MAP kinase-activating death domain (MADD) as the guanine nucleotide exchange factor for Rab27A and both Rab3 isoforms in primary human endothelial cells. Rab activity assays revealed a reduction in Rab27A, Rab3B, and Rab3D activation upon MADD silencing. Rab activation, but not binding, was dependent on the differentially expressed in normal and neoplastic cells (DENN) domain of MADD, indicating the potential existence of 2 Rab interaction modules. Furthermore, immunofluorescent analysis showed that Rab27A, Rab3B, and Rab3D recruitment to WPBs was dramatically decreased upon MADD knockdown, revealing that MADD drives Rab membrane targeting. Artificial mistargeting of MADD using a TOMM70 tag abolished Rab27A localization to WPB membranes in a DENN domain-dependent manner, indicating that normal MADD localization in the cytosol is crucial. Activation of Rab3B and Rab3D was reduced upon Rab27A silencing, suggesting that activation of these Rabs is enhanced through previous activation of Rab27A by MADD. MADD silencing did not affect WPB morphology, but it did reduce VWF intracellular content. Furthermore, MADD-depleted cells exhibited decreased histamine-evoked VWF release, similar to Rab27A-depleted cells. In conclusion, MADD acts as a master regulator of VWF secretion by coordinating the activation and membrane targeting of secretory Rabs to WPBs.
Indexed as
Identifiers
What OpenQuestion holds
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.