Practice question

Phosphatidylserine is normally confined to the cytoplasmic leaflet of the plasma membrane at greater than 85% asymmetry, maintained by P4-ATPase flippases ATP11A and ATP11C that use ATP to translocate aminophospholipids inward while floppases move lipids outward. Early in apoptosis, effector caspase-3 cleaves and inactivates flippases and simultaneously activates calcium-dependent scramblases such as Xkr8 and ANO6, causing rapid collapse of asymmetry and exposure of phosphatidylserine on the external surface. This externalized lipid functions as dominant eat-me signal recognized by dedicated phagocyte receptors TIM4, BAI1, stabilin-2, and MerTK via bridging molecule Gas6 stimulating Rac1-dependent cytoskeletal engulfment without release of proinflammatory cytokines. In vitro, Annexin V which binds phosphatidylserine in calcium-dependent manner marks apoptotic cells for flow cytometry detection. Sustained surface phosphatidylserine also provides catalytic surface for tenase and prothrombinase complexes in blood coagulation cascade. Failure to clear phosphatidylserine-positive apoptotic bodies contributes to systemic lupus-like autoimmunity, illustrating how lipid topology directly couples biochemistry to immune tolerance and homeostasis.