In animal cells, the plasma membrane exhibits an asymmetrical distribution of phospholipids, playing a crucial role in maintaining cellular function and integrity. Specifically, phosphatidylserine (PS) and phosphatidylethanolamine (PE) are located exclusively on the cytoplasmic leaflet, contributing to essential processes such as cell signaling. In contrast, phosphatidylcholine (PC) and sphingomyelin (SM) are found on the extracellular leaflet, where they play key roles in determining membrane physical properties and barrier functions. This phospholipid asymmetry is maintained by type IV P-type ATPases, such as ATP8A, ATP11A, and ATP11C, which specifically translocate PS and PE to the inner leaflet, preserving their asymmetry. However, despite PC and SM being the most abundant phospholipids in the plasma membrane and their significant roles in human diseases, the mechanisms regulating their distribution have remained unclear. We have recently identified a novel type of lipid-translocating membrane protein, TMEM63B, which responds to changes in membrane structures and controls the distribution of PC and SM in the plasma membrane. Interestingly, TMEM63B also has a mechanosensitive ion channel activity. This symposium aims to explore the molecular mechanisms that drive phospholipid asymmetry in the plasma membrane and discuss their implications for human diseases.
Katsumori Segawa (Sun,) studied this question.