Scientists at Kyoto University‘s Institute for Integrated Cell-Material Sciences (WPI-iCeMS) have discovered how cells control phospholipid distribution in their membranes.
Phospholipids, which form cell membrane bilayers, regulate molecule movement to maintain cell stability. They are usually unevenly distributed, with some on the inside and others on the outside.
Cells can quickly shift these lipids in response to signals, a process called phospholipid scrambling. This movement is crucial for functions like blood clotting and removing unwanted materials.
New research in Nature Communications found that specific protein complexes help cells move phospholipids. When calcium enters cells, it activates a protein complex that includes the ion channel Tmem63b and the vitamin B1 transporter Slc19a2. This process, called phospholipid scrambling, helps cells manage their membranes.
Professor Jun Suzuki, who led the study, explains that calcium triggers this scrambling. Han Niu, the study’s lead author, found that without Tmem63b, cells can’t scramble phospholipids in response to calcium.
Specific mutations in the Tmem63b gene, linked to conditions like epilepsy and anemia, cause scrambling all the time, even without calcium.
Researchers found that the potassium channel Kcnn4 also affects phospholipid scrambling. When either Slc19a2 or Kcnn4 was missing, the scrambling decreased. This shows that Tmem63b, Slc19a2, and Kcnn4 work together to control the process.
Earlier studies found other proteins involved but couldn’t explain everything. The discovery shows that Tmem63b and Slc19a2 work together as a pair, while other proteins work as pairs of the same protein.
Changes in the cell membrane’s tension might activate the Tmem63b/Slc19a2 complex. When calcium enters the cell and potassium leaves, the cell shrinks, altering membrane tension and helping activate Tmem63b. This mechanism may explain how cells adapt to changes through phospholipid scrambling.
The researchers hope these findings will help develop new treatments for diseases like epilepsy and anemia, where phospholipid scrambling is affected.
Journal reference:
- Niu, H., Maruoka, M., Noguchi, Y. et al. Phospholipid scrambling induced by an ion channel/metabolite transporter complex. Nature Communications. DOI: 10.1038/s41467-024-51939-w.