Lipids are components of the cell membrane, and count among their number the oft-villianized cholesterol, which is an integral component of the cell membrane. Many processes, such as the early development of multicellular organisms, depend on a cells ability to alter the lipid composition of its membrane. Controlling lipid production is of the utmost importance in the liver, which not only makes lipids for its own cells but also exports them into the bloodstream so they can be used elsewhere. When normal hepatic lipid metabolism is disrupted, it can lead to diseases such as atherosclerosis and developmental brain defects.
Some of the steps controlling how lipids are made within a cell are known. A set of factors called SREBPs (for sterol regulatory element binding proteins) are synthesized in the endoplasmic reticulum (ER) of the cell. When lipid production is required, SREBPs are transported into another cell organelle, the Golgi apparatus,where they are cleaved and thereby activated. These small fragments enter the cell nucleus, and control the activity of genes needed to make lipids. It is known that SCAPs (for SREBP cleavage-activating proteins) bind to SREBPs in the ER and escort the SREBPs to the golgi for cleavage, but exactly how SCAPs workand to what signals they respondis also not clear.
Work by Joseph L. Goldstein, Michael S. Brown and colleagues at the University of Texas Southwestern Medical Center offers new evidence as to the role of SCAPs. The researchers specifically inhibited the function of SCAP in the liver of mice. They found that the overall synthesis of lipids in the liver was reduced by 80% under normal conditions, indicating that SCAP is necessary for the basic mechanism of lipid production. Moreover, deprivation of normal dietary intake of lipidsa condition that normally would cause a massive up-regulation of lipid production-did not result in a significant increase. These findings show that SCAP is necessary for the norma
Contact: Nora Poppito
Cold Spring Harbor Laboratory