Proteolysis leads to the appearance of the long form of β3-endonexin in human platelets

Sadoul, Karin; Vignoud, Lucile; Mossuz, Pascal; Block, Marc R.

doi:10.1016/j.yexcr.2005.02.003

Cited by 3 publications

(2 citation statements)

References 30 publications

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“…Calpains have been implicated in the generation of the long form of β3-endonexin [56], proteolysis of platelet endothelial cell adhesion molecule-1 [57], vinculin [13], plasma membrane Ca 2+ ATPase [58], phosphatidylinositol phosphate kinase [59], and activation of calcineurin, a serine-threonine phosphatase [60]. The physiological significance of these findings remains to be explored in future studies.…”

Section: Other Calpain Substrates In Plateletsmentioning

confidence: 99%

Calpain-mediated regulation of platelet signaling pathways

Kuchay

Chishti

2007

Current Opinion in Hematology

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Purpose of review-There is considerable interest in understanding the function and mechanism of calpains in platelet aggregation, spreading, and granular secretion pathways. Recent insights from the calpain-1 knockout platelets suggest a pivotal role of these cysteine proteases in the regulation of outside-in signaling, aggregation, and clot retraction.Recent findings-The calpain-1 knockout mouse provided direct evidence for the role of calpain-1 in platelet aggregation and clot retraction. Reduced tyrosine phosphorylation of platelet proteins correlated with reduced platelet aggregation and clot retraction. Future investigations of the mechanism of platelet defects in calpain-1 null mice may unveil the physiological functions of this important and elusive protease in mammalian cells.Summary-This review focuses on the role of calpains in platelets with a particular emphasis on recent findings in calpain-1 null platelets. Previous studies used synthetic inhibitors to study the role of calpains in platelet function yielding useful information about the identification of calpain substrates. The development of calpain-1 null mice demonstrated that calpain-1 plays an important function in the regulation of platelet aggregation and clot retraction. Since the combined deletion of calpain-1 and calpain-2 genes results in embryonic lethality, the calpain-1 null mouse remains the only experimental model available to study the physiological role of calpains in mammalian cells.

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Section: Other Calpain Substrates In Plateletsmentioning

confidence: 99%

Calpain-mediated regulation of platelet signaling pathways

Kuchay

Chishti

2007

Current Opinion in Hematology

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“…β3-Endonexin is present in resting human platelets. Nonetheless, there is little available information about how β3-endonexin regulates integrin αIIbβ3 [91, 92]. CIB1 can disrupt the association of αIIb and β3 by binding to the αIIb cytoplasmic tail, which in turn activates integrin αIIbβ3 [83, 93].…”

Section: Integrin αIibβ3 Inside-out Signalingmentioning

confidence: 99%

Platelet integrin αIIbβ3: signal transduction, regulation, and its therapeutic targeting

et al. 2019

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Integrins are a family of transmembrane glycoprotein signaling receptors that can transmit bioinformation bidirectionally across the plasma membrane. Integrin αIIbβ3 is expressed at a high level in platelets and their progenitors, where it plays a central role in platelet functions, hemostasis, and arterial thrombosis. Integrin αIIbβ3 also participates in cancer progression, such as tumor cell proliferation and metastasis. In resting platelets, integrin αIIbβ3 adopts an inactive conformation. Upon agonist stimulation, the transduction of inside-out signals leads integrin αIIbβ3 to switch from a low-to high-affinity state for fibrinogen and other ligands. Ligand binding causes integrin clustering and subsequently promotes outside-in signaling, which initiates and amplifies a range of cellular events to drive essential platelet functions such as spreading, aggregation, clot retraction, and thrombus consolidation. Regulation of the bidirectional signaling of integrin αIIbβ3 requires the involvement of numerous interacting proteins, which associate with the cytoplasmic tails of αIIbβ3 in particular. Integrin αIIbβ3 and its signaling pathways are considered promising targets for antithrombotic therapy. This review describes the bidirectional signal transduction of integrin αIIbβ3 in platelets, as well as the proteins responsible for its regulation and therapeutic agents that target integrin αIIbβ3 and its signaling pathways.

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LncRNA NR_045147 modulates osteogenic differentiation and migration in PDLSCs via ITGB3BP degradation and mitochondrial dysfunction

Long,

Zhang,

et al. 2024

Stem Cells Translational Medicine

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Periodontitis is an inflammation of the alveolar bone and soft tissue surrounding the teeth. Although mesenchymal stem cells (MSCs) have been implicated in periodontal regeneration, the mechanisms by which they promote osteogenesis remain unclear. We examined whether epigenetic modifications mediated by the long-noncoding RNA (lncRNA) NR_045147, which plays a crucial role in cancer, influence the osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Alkaline phosphatase staining, alizarin red staining, and western blotting were used to detect the effects of NR_045147 on PDLSC osteogenic differentiation. Scratch migration and transwell chemotaxis assays were used to evaluate the effects of NR_045147 on PDLSC migration. Mitochondrial function was evaluated via Seahorse XF analysis to measure changes in cellular respiration upon manipulation of NR_045147 expression. Ubiquitination assays were performed to examine the protein stability and degradation pathways affected by the NR_045147–MDM2 interaction. An in vivo nude rat calvarial defect model was established and gene-edited PDLSCs were re-implanted to examine the osteogenic effects of NR_045147. NR_045147 significantly reduced PDLSC osteogenic differentiation and migration ability both in vitro and in vivo. Under inflammatory conditions, the loss of NR_045147 rescued osteogenesis. NR_045147 significantly blocked the expression of integrin beta3-binding protein (ITGB3BP). Mechanistically, NR_045147 promoted the ITGB3BP-MDM2 interaction, thus increasing ITGB3BP ubiquitination and degradation. NR_045147 regulated PDLSC mitochondrial respiration and ITGB3BP upregulation efficiently promoted their osteogenic differentiation and migration ability. Concluding, NR_045147 downregulation enhances PDLSC osteogenic differentiation and migration, connects changes in cellular metabolism to functional outcomes via mitochondrial respiration, and promotes ITGB3BP degradation by mediating its interaction with MDM2.

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Proteolysis leads to the appearance of the long form of β3-endonexin in human platelets

Cited by 3 publications

References 30 publications

Calpain-mediated regulation of platelet signaling pathways

Calpain-mediated regulation of platelet signaling pathways

Platelet integrin αIIbβ3: signal transduction, regulation, and its therapeutic targeting

LncRNA NR_045147 modulates osteogenic differentiation and migration in PDLSCs via ITGB3BP degradation and mitochondrial dysfunction

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