ArticleHaematologica2016
Cytoskeletal perturbation leads to platelet dysfunction and thrombocytopenia in variant forms of Glanzmann thrombasthenia.
Article in Haematologica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 58 citations in OpenAlex.
- Inherited Platelet GPIV Deficiency: First Description of a Series of Unrelated Patients with Bleeding Diathesis.Biomolecules · 2026Article
- Clinical and Genetic Characterization of 269 Patients With Suspected Inherited Platelet Disorders: The Padua Monocentric Experience.International journal of laboratory hematology · 2026Article
- The co-inheritance of twoHaematologica · 2026Article
- ITGA2B/ITGB3-Related Macrothrombocytopenia Associated With Gain-of-Function Mutations in ITGA2B or ITGB3 Genes.Journal of cellular and molecular medicine · 2026Review
- Matrix stiffness controls megakaryocyte adhesion, fibronectin fibrillogenesis, and proplatelet formation through Itgβ3.Blood advances · 2023Article
- Platelet dysfunction in platelet-type von Willebrand disease due to the constitutive triggering of the Lyn-PECAM1 inhibitory pathway.Haematologica · 2022Article
- Cucurbitacins Elicit Anti-Platelet Activity via Perturbation of the Cytoskeleton and Integrin Function.Thrombosis and haemostasis · 2022Article
- Rasa3 deficiency minimally affects thrombopoiesis but promotes severe thrombocytopenia due to integrin-dependent platelet clearance.JCI insight · 2022Article
- A p.Arg127Gln variant in GPIbα LRR5 allosterically enhances affinity for VWF: a novel form of platelet-type VWD.Blood advances · 2022Article
- Quantitative LC-MS/MS uncovers the regulatory role of autophagy in immune thrombocytopenia.Cancer cell international · 2021Article
- Essential role of zyxin in platelet biogenesis and glycoprotein Ib-IX surface expression.Cell death & disease · 2021Article
- Significant reductions in apoptosis-related proteins (HSPA6, HSPA8, ITGB3, YWHAH, and PRDX6) are involved in immune thrombocytopenia.Journal of thrombosis and thrombolysis · 2021Article
- Learning the Ropes of Platelet Count Regulation: Inherited Thrombocytopenias.Journal of clinical medicine · 2021Review
- TMEA, a Polyphenol inFrontiers in cell and developmental biology · 2021Article
- Inherited thrombocytopenias: history, advances and perspectives.Haematologica · 2020Review
- Diagnosis of Inherited Platelet Disorders on a Blood Smear.Journal of clinical medicine · 2020Article
- β4GALT1 controls β1 integrin function to govern thrombopoiesis and hematopoietic stem cell homeostasis.Nature communications · 2020Article
- Modulating Integrin αIIbβ3 Activity through Mutagenesis of Allosterically Regulated Intersubunit Contacts.Biochemistry · 2019Article
- Mechanisms of thrombocytopenia in platelet-type von Willebrand disease.Haematologica · 2019Article
- Microtubule polyglutamylation and acetylation drive microtubule dynamics critical for platelet formation.BMC biology · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Several patients have been reported to have variant dominant forms of Glanzmann thrombasthenia, associated with macrothrombocytopenia and caused by gain-of-function mutations of ITGB3 or ITGA2B leading to reduced surface expression and constitutive activation of integrin αIIbβ3. The mechanisms leading to a bleeding phenotype of these patients have never been addressed. The aim of this study was to unravel the mechanism by which ITGB3 mutations causing activation of αIIbβ3 lead to platelet dysfunction and macrothrombocytopenia. Using platelets from two patients carrying the β3 del647-686 mutation and Chinese hamster ovary cells expressing different αIIbβ3-activating mutations, we showed that reduced surface expression of αIIbβ3 is due to receptor internalization. Moreover, we demonstrated that permanent triggering of αIIbβ3-mediated outside-in signaling causes an impairment of cytoskeletal reorganization arresting actin turnover at the stage of polymerization. The induction of actin polymerization by jasplakinolide, a natural toxin that promotes actin nucleation and prevents depolymerization of stress fibers, in control platelets produced an impairment of platelet function similar to that of patients with variant forms of dominant Glanzmann thrombasthenia. del647-686β3-transduced murine megakaryocytes generated proplatelets with a reduced number of large tips and asymmetric barbell-proplatelets, suggesting that impaired cytoskeletal rearrangement is the cause of macrothrombocytopenia. These data show that impaired cytoskeletal remodeling caused by a constitutively activated αIIbβ3 is the main effector of platelet dysfunction and macrothrombocytopenia, and thus of bleeding, in variant forms of dominant Glanzmann thrombasthenia.
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