The latest research by Associate Professor Lyu Pengfei’s group at SLST has found that the traditional tight junction component Occludin plays a crucial regulatory role in lipid droplet secretion, one of the fundamental cellular behaviors. On January 18th, 2022, the work from Lyu's lab was published online in PLOS Biology, in an article entitled “Occludin is a target of Src kinase and promotes lipid secretion by binding to BTN1a1 and XOR”.
Lipid droplets have gained increasing recognition as a new organelle essential for various fundamental cellular processes, including lipid trafficking, vesicular transport, and metabolism. Although much knowledge has been accumulated in the field of lipid synthesis and degradation, little is known about the kinetic regulation of lipid droplets, including their formation, maintenance, and secretion. The lipid-secreting behavior is present in various organs, including the mammary gland and liver. When liver lipid secretion is abnormal, it will lead to the occurrence and development of metabolic diseases such as the fatty liver. The mammary gland is capable of secreting milk containing many lipids. However, the mechanisms regulating lipid droplet secretion in the mammary gland are poorly understood.
Lyu's lab found that Occludin-deficient mice have lipid metabolism defects. Further experiments found that the volume of lipid droplets in Occludin knockout mammary gland cells was larger than normal. The change in lipid droplet size was not caused by abnormal lipid synthesis or degradation but rather by the failure of lipid droplet secretion. They also found that Occludin locates on the lipid droplet membrane after lipid droplet formation. Subsequent experiments proved that Occludin is a downstream target of Src kinase and promotes lipid droplet secretion by binding to lipid droplet regulatory proteins BTN1a1 and XOR. This work not only provides a new mechanism for understanding the production, transportation, and secretion of lipid droplets but also provides a theoretical basis and therapeutic targets for the study of various diseases caused by the loss of Occludin, such as brain calcification, hearing loss, infertility, and digestive tract abnormalities, etc.
Associate Research Professor Lyu Yunzhe and two Ph.D. students of the Class of 2021, Zhou Tao and Xu Chongshen, are co-first authors. Prof. Lyu Pengfei is the corresponding author of this study.
The process of lipid droplet secretion in mammary epithelial cells. In wild-type cells (green background), Occludin promotes rapid and efficient secretion of the synthesized lipid droplets. However, in mutant cells (grey background), lipid droplets could not be efficiently secreted out of the cell, leading to accumulation within the cell and ultimately to the cessation of milk production.