Scientists at Kyoto University’s Institute for Integrated Cell-Material Sciences (WPI-iCeMS) have made significant strides in understanding how cells regulate the distribution of lipids in their cell membrane. Lipids, specifically phospholipids, are crucial for maintaining a stable internal environment within cells. These phospholipids are organized in a bilayer structure in the cell membrane, controlling the movement of molecules in and out of the cell.
Typically, phospholipids are unevenly distributed across the cell membrane, with different types located on the inner and outer sides. However, cells need to quickly alter this distribution in response to various signals. This movement of phospholipids from one side of the membrane to the other, known as phospholipid scrambling, plays a vital role in processes like blood clotting and cell removal.
The recent study, published in Nature Communications, sheds light on the role of protein complexes in facilitating phospholipid scrambling. The researchers identified a specific protein complex consisting of the ion channel Tmem63b and the vitamin B1 transporter Slc19a2 that triggers phospholipid scrambling in response to calcium signals within the cell.
Professor Jun Suzuki, the lead researcher, highlighted the importance of calcium in activating cellular processes like phospholipid scrambling. The study found that the absence of Tmem63b resulted in a loss of calcium-induced phospholipid scrambling activity in cells. Interestingly, mutations in the Tmem63b gene associated with conditions such as epilepsy and anemia led to continuous activation of phospholipid scrambling, independent of calcium levels.
Moreover, the researchers discovered that another protein, Kcnn4, a potassium channel activated by calcium, also influences phospholipid scrambling. When either Slc19a2 or Kcnn4 was missing, the process of phospholipid scrambling was impaired. This underscores the collaborative role of Tmem63b, Slc19a2, and Kcnn4 in regulating phospholipid distribution.
The study further revealed that changes in the tension of the cell’s plasma membrane could contribute to activating the Tmem63b/Slc19a2 complex. The entry of calcium and exit of potassium ions induce cell shrinkage, altering membrane tension and facilitating the activation of Tmem63b. This mechanism may explain how neuronal cells and red blood cells adapt to environmental changes through phospholipid scrambling.
Looking ahead, the researchers aim to leverage these findings to develop novel treatments for conditions characterized by disrupted phospholipid scrambling, such as epilepsy and anemia. By unraveling the intricate mechanisms governing lipid distribution in cell membranes, this research opens new avenues for therapeutic interventions targeting these processes.
In conclusion, the study’s findings offer a deeper understanding of how proteins regulate the cell membrane and pave the way for innovative treatments in the realm of cellular biology and disease management.