ArticleBlood2015
VPS33B regulates protein sorting into and maturation of α-granule progenitor organelles in mouse megakaryocytes.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 61 citations in OpenAlex.
- α-Actinin-1 in Megakaryocytes: Its Structure, Interacting Proteins and Implications for Thrombopoiesis.Biomedicines · 2025Review
- α-Actinin-1 deficiency in megakaryocytes causes low platelet count, platelet dysfunction, and mitochondrial impairment.Blood advances · 2025Article
- Epidermal lamellar bodies, essential organelles for the skin barrier.Frontiers in cell and developmental biology · 2025Review
- Overlapping Machinery in Lysosome-Related Organelle Trafficking: A Lesson from Rare Multisystem Disorders.Cells · 2022Review
- Sorting nexin 24 is required for α-granule biogenesis and cargo delivery in megakaryocytes.Haematologica · 2022Article
- Diversification of CORVET tethers facilitates transport complexity inJournal of cell science · 2020Article
- FERARI is required for Rab11-dependent endocytic recycling.Nature cell biology · 2020Article
- A Novel Mutation ofCase reports in genetics · 2020Article
- Mechanism of platelet α-granule biogenesis: study of cargo transport and the VPS33B-VPS16B complex in a model system.Blood advances · 2019Article
- The road to lysosome-related organelles: Insights from Hermansky-Pudlak syndrome and other rare diseases.Traffic (Copenhagen, Denmark) · 2019Review
- A novel mutation inJIMD reports · 2019Article
- Sorting machineries: how platelet-dense granules differ from α-granules.Bioscience reports · 2018Review
- Severe renal Fanconi and management strategies in Arthrogryposis-Renal dysfunction-Cholestasis syndrome: a case report.BMC nephrology · 2018Article
- Clinical pharmacology in Stockholm 50 years-report from the jubilee symposium.European journal of clinical pharmacology · 2018Article
- VPS33B and VIPAR are essential for epidermal lamellar body biogenesis and function.Biochimica et biophysica acta. Molecular basis of disease · 2018Article
- The life cycle of platelet granules.F1000Research · 2018Review
- The ins and outs of endocytic trafficking in platelet functions.Current opinion in hematology · 2017Review
- Vps33b is crucial for structural and functional hepatocyte polarity.Journal of hepatology · 2017Article
- Autosomal Recessive Keratoderma-Ichthyosis-Deafness (ARKID) Syndrome Is Caused by VPS33B Mutations Affecting Rab Protein Interaction and Collagen Modification.The Journal of investigative dermatology · 2017Review
- Review
Corrections and comments
- Commented on by
Authors and funding
14 authors at 8 institutions in 4 countries.
Funding
Abstract
Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is caused by deficiencies in the trafficking proteins VPS33B or VIPAR, and is associated with a bleeding diathesis and a marked reduction in platelet α-granules. We generated a tamoxifen-inducible mouse model of VPS33B deficiency, Vps33b(fl/fl)-ER(T2), and studied the platelet phenotype and α-granule biogenesis. Ultrastructural analysis of Vps33b(fl/fl)-ER(T2) platelets identified a marked reduction in α-granule count and the presence of small granule-like structures in agreement with the platelet phenotype observed in ARC patients. A reduction of ∼65% to 75% was observed in the α-granule proteins von Willebrand factor and P-selectin. Although platelet aggregation responses were not affected, a defect in δ-granule secretion was observed. Under arteriolar shear conditions, Vps33b(fl/fl)-ER(T2) platelets were unable to form stable aggregates, and tail-bleeding measurement revealed a bleeding diathesis. Analysis of bone marrow-derived megakaryocytes (MKs) by conventional and immuno-electron microscopy from Vps33b(fl/fl)-ER(T2) mice revealed a reduction in mature type-II multivesicular bodies (MVB II) and an accumulation of large vacuoles. Proteins that are normally stored in α-granules were underrepresented in MVB II and proplatelet extensions. These results demonstrate that abnormal protein trafficking and impairment in MVB maturation in MKs underlie the α-granule deficiency in Vps33b(fl/fl)-ER(T2) mouse and ARC patients.
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.