BSB PhD Exit Seminar: Phospholipid Flippases in B cells and Platelets

Phosphatidylserine (PS) is predominantly confined to the inner leaflet of the plasma membrane in eukaryotes through the action of ATP-dependent phospholipid-transporting flippases. PS can be exposed on the cell surface by scramblases in apoptotic cells and activated platelets. PS exposure is indispensable for clearance of dead cells and procoagulant function of platelets. Scramblase activity alone is insufficient to support stable PS exposure; inactivation of flippases is also required to prevent PS from being re-internalised.

In my PhD I investigated the biochemical properties and physiological role of the aminophospholipid flippases ATP11C and ATP8A1. Using ATP11C-deficient mice, I could demonstrate that 1) ATP11C acted as a major PS selective flippase in B cells; 2) ATP11C was not the acting flippase in platelets, but platelets from ATP11C-deficient mice showed reduced life span and increased size. Moreover, I identified ATP8A1 as a major flippase in mouse platelets and revealed that it was inactivated through calpain-mediated cleavage during platelet apoptosis. These findings extend our understanding on the role of flippases in B cell development and important mechanisms of platelet survival and thrombosis.