New Protein Complex Discovered in Cell Membrane Lipid Regulation

Researchers at Kyoto University's Institute for Integrated Cell-Material Sciences have identified a novel protein complex involved in phospholipid scrambling, a crucial cellular process. The study, published in Nature Communications, reveals that a complex comprising the ion channel Tmem63b and the vitamin B1 transporter Slc19a2 plays a key role in redistributing phospholipids across cell membranes in response to calcium signals.

The team found that deleting Tmem63b eliminated calcium-induced phospholipid scrambling, while certain disease-linked mutations in Tmem63b caused continuous activation of this process. Additionally, the calcium-activated potassium channel Kcnn4 was shown to influence phospholipid scrambling.

This discovery builds on previous research by the same group, which had identified other proteins involved in phospholipid scrambling. The new findings demonstrate that Tmem63b and Slc19a2 function as a heterodimer, unlike previously identified scramblases that operate as homodimers.

The researchers also proposed a mechanism by which changes in cell membrane tension, caused by ion flux, might activate the Tmem63b/Slc19a2 complex. This could explain how neuronal and red blood cells adapt to environmental changes through phospholipid scrambling.

These insights into the regulation of cell membrane lipid distribution could potentially lead to new treatments for diseases associated with disrupted phospholipid scrambling, such as epilepsy and anemia.