ArticleBlood2023
Proximity proteomics identifies septins and PAK2 as decisive regulators of actomyosin-mediated expulsion of von Willebrand factor.
Article in Blood, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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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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.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Endothelial β-PIX (ARHGEF7) supports actomyosin mediated expulsion of VWF through dynamic reorganization of the cytoskeleton.Molecular biology of the cell · 2026Article
- RAB5C Increases Endothelial Release of VWF by Regulating Vesicle Trafficking.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- RalB uncoupling from exocyst is required for endothelial Weibel-Palade body exocytosis.Molecular biology of the cell · 2025Article
- Identification of multiple novel procoagulant plasma ligands for stabilin-2.Journal of thrombosis and haemostasis : JTH · 2025Article
- Weibel-Palade bodies: function and role in thrombotic thrombocytopenic purpura and in diarrhea phase of STEC-hemolytic uremic syndrome.Pediatric nephrology (Berlin, Germany) · 2025Review
- Weibel-Palade bodies - secretory organelles at the interface of inflammation and hemostasis.Frontiers in cell and developmental biology · 2025Review
- Regulation of Vascular Injury and Repair by P21-Activated Kinase 1 and P21-Activated Kinase 2: Therapeutic Potential and Challenges.Biomolecules · 2024Review
- Myosin-1C augments endothelial secretion of von Willebrand factor by linking contractile actomyosin machinery to the plasma membrane.Blood advances · 2024Article
- Myo1c drives actin-dependent VWF expulsion from EC WPBs.Blood advances · 2024Article
- Venous thromboembolic disease genetics: from variants to function.Journal of thrombosis and haemostasis : JTH · 2024Review
- The proteomic landscape of in vitro cultured endothelial cells across vascular beds.Communications biology · 2024Article
- Evoked Weibel-Palade Body Exocytosis Modifies the Endothelial Cell Surface by Releasing a Substrate-Selective Phosphodiesterase.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Review
- Review
- The emerging role of septins in fungal pathogenesis.Cytoskeleton (Hoboken, N.J.)Review
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
In response to tissue injury, within seconds the ultra-large glycoprotein von Willebrand factor (VWF) is released from endothelial storage organelles (Weibel-Palade bodies) into the lumen of the blood vasculature, where it leads to the recruitment of platelets. The marked size of VWF multimers represents an unprecedented burden on the secretory machinery of endothelial cells (ECs). ECs have evolved mechanisms to overcome this, most notably an actomyosin ring that forms, contracts, and squeezes out its unwieldy cargo. Inhibiting the formation or function of these structures represents a novel therapeutic target for thrombotic pathologies, although characterizing proteins associated with such a dynamic process has been challenging. We have combined APEX2 proximity labeling with an innovative dual loss-of-function screen to identify proteins associated with actomyosin ring function. We show that p21 activated kinase 2 (PAK2) recruits septin hetero-oligomers, a molecular interaction that forms a ring around exocytic sites. This cascade of events controls actomyosin ring function, aiding efficient exocytic release. Genetic or pharmacological inhibition of PAK2 or septins led to inefficient release of VWF and a failure to form platelet-catching strings. This new molecular mechanism offers additional therapeutic targets for the control of thrombotic disease and is highly relevant to other secretory systems that employ exocytic actomyosin machinery.
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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.