Calpain cleaves phospholipid flippase ATP8A1 during apoptosis in platelets.
Blood Adv
; 3(3): 219-229, 2019 02 12.
Article
em En
| MEDLINE
| ID: mdl-30674456
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfolipídeos
/
Plaquetas
/
Calpaína
/
Adenosina Trifosfatases
/
Proteínas de Transferência de Fosfolipídeos
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article