Fig. 5

The model of PtdSer exposure on the surface of activated platelets. In the plasma membrane, flippases (ATP11C and ATP11A) specifically flip PtdSer from the outer leaflet of the lipid bilayer to the inner leaflet, forming an asymmetric distribution on the plasma membrane [43], while scramblase TMEM16F is inactive [44]. Once platelets are activated by thrombin, the concentration of Ca²⁺ in the activated platelets increases temporarily [45], instantly activates the scramblase activity of TMEM16F [44], inactivates the flippase activity of ATP11A and ATP11C [41], and quickly expose PtdSer on the surface of platelets. Once the platelets return to the normal state, the level of Ca²⁺ in the platelets decreases, which inactivates TMEM16F, restores the flippase activity of ATP11A and ATP11C [43], and re-establishes the asymmetric distribution of PtdSer in the plasma membrane. In short, Ca²⁺-induced PtdSer exposure is reversible