ArticleBlood2013
Platelets lacking PIP5KIγ have normal integrin activation but impaired cytoskeletal-membrane integrity and adhesion.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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
16 citing papers in PubMed, 21 citations in OpenAlex.
- The phosphatidylinositol-5' phosphatase synaptojanin1 limits integrin-mediated invasion ofMicrobiology spectrum · 2024Article
- A Plethora of Functions Condensed into Tiny Phospholipids: The Story of PI4P and PI(4,5)PCells · 2023Review
- The platelet transcriptome and proteome in Alzheimer's disease and aging: an exploratory cross-sectional study.Frontiers in molecular biosciences · 2023Article
- Review of PIP2 in Cellular Signaling, Functions and Diseases.International journal of molecular sciences · 2020Review
- A multiscale biophysical model for the recruitment of actin nucleating proteins at the membrane interface.Soft matter · 2020Article
- Cooperative PSGL-1 and CXCR2 signaling in neutrophils promotes deep vein thrombosis in mice.Blood · 2018Article
- Selectins and chemokines use shared and distinct signals to activate β2 integrins in neutrophils.Blood advances · 2018Article
- Phosphatidylinositol transfer protein-α in platelets is inconsequential for thrombosis yet is utilized for tumor metastasis.Nature communications · 2017Article
- Phosphatidylinositol 4,5-Bisphosphate Modulates the Affinity of Talin-1 for Phospholipid Bilayers and Activates Its Autoinhibited Form.Biochemistry · 2016Article
- n-3 polyunsaturated fatty acids suppress CD4(+) T cell proliferation by altering phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] organization.Biochimica et biophysica acta · 2016Article
- The class II PI 3-kinase, PI3KC2α, links platelet internal membrane structure to shear-dependent adhesive function.Nature communications · 2015Article
- Article
- Phosphatidylinositol 4,5-bisphosphate triggers activation of focal adhesion kinase by inducing clustering and conformational changes.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Article
- Platelet lipidomics: modern day perspective on lipid discovery and characterization in platelets.Circulation research · 2014Review
- Review
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
Abstract
Three isoforms of phosphatidylinositol-4-phosphate 5-kinase (PIP5KIα, PIP5KIβ, and PIP5KIγ) can each catalyze the final step in the synthesis of phosphatidylinositol-4,5-bisphosphate (PIP2), which in turn can be either converted to second messengers or bind directly to and thereby regulate proteins such as talin. A widely quoted model speculates that only p90, a longer splice form of platelet-specific PIP5KIγ, but not the shorter p87 PIP5KIγ, regulates the ligand-binding activity of integrins via talin. However, when we used mice genetically engineered to lack only p90 PIP5KIγ, we found that p90 PIP5KIγ is not critical for integrin activation or platelet adhesion on collagen. However, p90 PIP5KIγ-null platelets do have impaired anchoring of their integrins to the underlying cytoskeleton. Platelets lacking both the p90 and p87 PIP5KIγ isoforms had normal integrin activation and actin dynamics, but impaired anchoring of their integrins to the cytoskeleton. Most importantly, they formed weak shear-resistant adhesions ex vivo and unstable vascular occlusions in vivo. Together, our studies demonstrate that, although PIP5KIγ is essential for normal platelet function, individual isoforms of PIP5KIγ fulfill unique roles for the integrin-dependent integrity of the membrane cytoskeleton and for the stabilization of platelet adhesion.
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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.