Regulation of secretion, exocytosis and membrane fusion by vesicular lipids

点击翻译按钮获取中文摘要

Many molecules (e.g. hormones) that are secreted by cells for communications between cells are packaged into small vesicles (each surrounded by a lipid membrane that includes lots of cholesterol) within the cell. The secretion of the packaged signaling molecules from a cell involves the fusion of the vesicle with the cell's surface (which is also surrounded by a lipid membrane whose density of cholesterol is about 1/3 that of the vesicular membrane); this process starts with the formation of a very small pore that connects the inside of a vesicle with the cell's surface. My lab recently discovered that total amount of cholesterol in cells can regulate the slow trickle of hormones from a cell when a vesicle just starts to fuse with the cell's surface. However we are uncertain whether the cholesterol in the membrane of the vesicle or the cell surface plays a more prominent role in this effect. Here we propose to clarify this issue by exploiting a genetic manipulation that can selectively reduce cholesterol in the membrane of the secretory vesicles, but not the cell surface. The results from the proposed study will allow us to better understand why cells have evolved to naturally accumulate cholesterol at certain membrane compartments. The trainees involved in the proposed study will learn not only the genetic and molecular tools to manipulate the distribution of cholesterol molecules in cells, but also the biophysical tools to trigger and monitor secretion from individual cells.