ArticleBlood advances2019
Calpain cleaves phospholipid flippase ATP8A1 during apoptosis in platelets.
Article in Blood advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Calpain inhibition by calpeptin modulates adipocyte lipid metabolism and secretome-mediated inflammatory crosstalk with hepatocytes.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Substrates, regulation, cellular functions, and disease associations of P4-ATPases.Communications biology · 2025Review
- ATP11C promotes the differentiation of pre-B cells into immature B cells but does not affect their IL-7-dependent proliferation.Immunologic research · 2023Article
- Platelet-Derived Extracellular Vesicles in Arterial Thrombosis.Advances in experimental medicine and biology · 2023Article
- Early Epigenetic Responses in the Genomic DNA Methylation Fingerprints in Cells in Response to Sublethal Exposure of Silver Nanoparticles.Frontiers in bioengineering and biotechnology · 2022Article
- Lipid flippases as key players in plant adaptation to their environment.Nature plants · 2021Review
- Usnic Acid andAntioxidants (Basel, Switzerland) · 2021Article
- Breakdown in membrane asymmetry regulation leads to monocyte recognition of P. falciparum-infected red blood cells.PLoS pathogens · 2021Article
- Reduction in flippase activity contributes to surface presentation of phosphatidylserine in human senescent erythrocytes.Journal of cellular and molecular medicine · 2020Article
- 2-Aminoethoxydiphenylborate (2-APB) inhibits release of phosphatidylserine-exposing extracellular vesicles from platelets.Cell death discovery · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The asymmetric distribution of phospholipids in the plasma/organellar membranes is generated and maintained through phospholipid flippases in resting cells, but becomes disrupted in apoptotic cells and activated platelets, resulting in phosphatidylserine (PS) exposure on the cell surface. Stable PS exposure during apoptosis requires inactivation of flippases to prevent PS from being reinternalized. Here we show that flippase ATP8A1 is highly expressed in both murine and human platelets, but is not present in the plasma membrane. ATP8A1 is cleaved by the cysteine protease calpain during apoptosis, and the cleavage is prevented indirectly by caspase inhibition, involving blockage of calcium influx into platelets and subsequent calpain activation. In contrast, in platelets activated with thrombin and collagen and exposing PS, ATP8A1 remains intact. These data reveal a novel mechanism of flippase cleavage and suggest that flippase activity in intracellular membranes differs between platelets undergoing apoptosis and activation.
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