ArticleMolecular and cellular biology2001
Disruption of the mouse mu-calpain gene reveals an essential role in platelet function.
Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 238 citations in OpenAlex.
- Regulation of cell adhesion and migration by Kindlin-3 cleavage by calpain.The Journal of biological chemistry · 2012Trial
- Cross-species comparison of platelet proteomes reveals developmentally regulated metabolic and inflammatory changes.Blood vessels, thrombosis & hemostasis · 2026Article
- Subtype-specific divergent roles of calpain-1 and calpain-2 in basal A triple-negative breast cancer.BMC molecular and cell biology · 2025Article
- Calpain1 inhibition enhances autophagy-lysosomal pathway and ameliorates tubulointerstitial fibrosis in Nephronophthisis.Molecular medicine (Cambridge, Mass.) · 2025Article
- Protein tyrosine phosphatase 1B in metabolic diseases and drug development.Nature reviews. Endocrinology · 2024Review
- A cysteine proteinase inhibitor ALLN alleviates bleomycin-induced skin and lung fibrosis.Arthritis research & therapy · 2023Article
- Therapeutic use of calpeptin in COVID-19 infection.Clinical science (London, England : 1979) · 2022Article
- Human Protein Tyrosine Phosphatase 1B (PTP1B): From Structure to Clinical Inhibitor Perspectives.International journal of molecular sciences · 2022Review
- Co-expression analysis to identify key modules and hub genes associated with COVID-19 in platelets.BMC medical genomics · 2022Article
- Calpains as Potential Therapeutic Targets for Myocardial Hypertrophy.International journal of molecular sciences · 2022Review
- Calpain-1 inhibition attenuates in vivo thrombosis in a humanized model of sickle cell disease.Thrombosis research · 2022Article
- Cleavage of talin by calpain promotes platelet-mediated fibrin clot contraction.Blood advances · 2021Article
- Photoreceptor Cell Calcium Dysregulation and Calpain Activation Promote Pathogenic Photoreceptor Oxidative Stress and Inflammation in Prodromal Diabetic Retinopathy.The American journal of pathology · 2021Article
- The role of cGMP-signalling and calcium-signalling in photoreceptor cell death: perspectives for therapy development.Pflugers Archiv : European journal of physiology · 2021Review
- Ginsenoside Rk1 suppresses platelet mediated thrombus formation by downregulation of granule release and αJournal of ginseng research · 2021Article
- Calpain-2 participates in the process of calpain-1 inactivation.Bioscience reports · 2020Article
- Calpain-1 ablation partially rescues disease-associated hallmarks in models of Machado-Joseph disease.Human molecular genetics · 2020Article
- Calpain proteolytic systems counteract endothelial cell adaptation to inflammatory environments.Inflammation and regeneration · 2020Review
- CRTH2 promotes endoplasmic reticulum stress-induced cardiomyocyte apoptosis through m-calpain.EMBO molecular medicine · 2018Article
- Interleukin-33 is activated by allergen- and necrosis-associated proteolytic activities to regulate its alarmin activity during epithelial damage.Scientific reports · 2018Article
30 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Conventional calpains are ubiquitous calcium-regulated cysteine proteases that have been implicated in cytoskeletal organization, cell proliferation, apoptosis, cell motility, and hemostasis. There are two forms of conventional calpains: the mu-calpain, or calpain I, which requires micromolar calcium for half-maximal activation, and the m-calpain, or calpain II, which functions at millimolar calcium concentrations. We evaluated the functional role of the 80-kDa catalytic subunit of mu-calpain by genetic inactivation using homologous recombination in embryonic stem cells. The mu-calpain-deficient mice are viable and fertile. The complete deficiency of mu-calpain causes significant reduction in platelet aggregation and clot retraction but surprisingly the mutant mice display normal bleeding times. No detectable differences were observed in the cleavage pattern and kinetics of calpain substrates such as the beta3 subunit of alphaIIbbeta3 integrin, talin, and ABP-280 (filamin). However, mu-calpain null platelets exhibit impaired tyrosine phosphorylation of several proteins including the beta3 subunit of alphaIIbbeta3 integrin, correlating with the agonist-induced reduction in platelet aggregation. These results provide the first direct evidence that mu-calpain is essential for normal platelet function, not by affecting the cleavage of cytoskeletal proteins but by potentially regulating the state of tyrosine phosphorylation of the platelet proteins.
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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.