ArticleNature communications2014
Loss of PIKfyve in platelets causes a lysosomal disease leading to inflammation and thrombosis in mice.
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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.
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.
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Who cites it
23 citing papers in PubMed, 53 citations in OpenAlex.
- Phase II trial of multi-tyrosine kinase inhibitor ESK981 in combination with PD-1 inhibitor nivolumab in patients with metastatic castration-resistant prostate cancer.Investigational new drugs · 2024Trial
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- Article
- Identification and Utilization of a Chemical Probe to Interrogate the Roles of PIKfyve in the Lifecycle of β-Coronaviruses.Journal of medicinal chemistry · 2022Article
- The Immunotherapy and Immunosuppressive Signaling in Therapy-Resistant Prostate Cancer.Biomedicines · 2022Review
- Signaling Through FcγRIIA and the C5a-C5aR Pathway Mediate Platelet Hyperactivation in COVID-19.Frontiers in immunology · 2022Article
- Loss of PIKfyve drives the spongiform degeneration in prion diseases.EMBO molecular medicine · 2021Article
- Dissecting lipid metabolism alterations in SARS-CoV-2.Progress in lipid research · 2021Review
- Phosphoinositides in autophagy: current roles and future insights.The FEBS journal · 2020Review
- PIKfyve Deficiency in Myeloid Cells Impairs Lysosomal Homeostasis in Macrophages and Promotes Systemic Inflammation in Mice.Molecular and cellular biology · 2019Article
- Biogenesis of lysosome-related organelles complex-1 (BORC) regulates late endosomal/lysosomal size through PIKfyve-dependent phosphatidylinositol-3,5-bisphosphate.Traffic (Copenhagen, Denmark) · 2019Article
- PIKfyve/Fab1 is required for efficient V-ATPase and hydrolase delivery to phagosomes, phagosomal killing, and restriction of Legionella infection.PLoS pathogens · 2019Article
- The Phosphoinositide Kinase PIKfyve Promotes Cathepsin-S-Mediated Major Histocompatibility Complex Class II Antigen Presentation.iScience · 2019Article
- Lysosome enlargement during inhibition of the lipid kinase PIKfyve proceeds through lysosome coalescence.Journal of cell science · 2018Article
- PIKfyve regulates melanosome biogenesis.PLoS genetics · 2018Article
- Unbiased Proteomics of Early Lewy Body Formation Model Implicates Active Microtubule Affinity-Regulating Kinases (MARKs) in Synucleinopathies.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Deletion of PIKfyve alters alveolar macrophage populations and exacerbates allergic inflammation in mice.The EMBO journal · 2017Article
- PI5P and PI(3,5)PCell structure and function · 2017Review
- Article
- Active vacuolar H+ ATPase and functional cycle of Rab5 are required for the vacuolation defect triggered by PtdIns(3,5)P2 loss under PIKfyve or Vps34 deficiency.American journal of physiology. Cell physiology · 2016Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
PIKfyve is essential for the synthesis of phosphatidylinositol-3,5-bisphosphate [PtdIns(3,5)P2] and for the regulation of endolysosomal membrane dynamics in mammals. PtdIns(3,5)P2 deficiency causes neurodegeneration in mice and humans, but the role of PtdIns(3,5)P2 in non-neural tissues is poorly understood. Here we show that platelet-specific ablation of PIKfyve in mice leads to accelerated arterial thrombosis, and, unexpectedly, also to inappropriate inflammatory responses characterized by macrophage accumulation in multiple tissues. These multiorgan defects are attenuated by platelet depletion in vivo, confirming that they reflect a platelet-specific process. PIKfyve ablation in platelets induces defective maturation and excessive storage of lysosomal enzymes that are released upon platelet activation. Impairing lysosome secretion from PIKfyve-null platelets in vivo markedly attenuates the multiorgan defects, suggesting that platelet lysosome secretion contributes to pathogenesis. Our findings identify PIKfyve as an essential regulator for platelet lysosome homeostasis, and demonstrate the contributions of platelet lysosomes to inflammation, arterial thrombosis and macrophage biology.
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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.