FLUORESCENT ANALYSIS OF REGULATION OF CHOLESTEROL METABOLISM IN MAMMALIAN CELL

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The major focus of our research program is to understand how cholesterol metabolism is regulated in higher animals. Cholesterol is a major structural molecule of the plasma membranes of virtually all mammalian cells. Its unique chemical and geometric qualities makes it ideal for its role in membrane function since it provides structural rigidity and aids in the selective permeability of the lipid bilayer. In addition, cholesterol plays an essential role in more specialized biological processes. It is a major component of the very low density lipoprotein particle which is secreted by the liver for delivery of cholesterol and triacylglycerols to other sites in the body; and cholesterol is a required precursor in the synthesis of steroid hormones and bile acids which are essential for proper nutrition, growth, and development. Also, the excellent insulating capacity of the cholesterol molecule is exploited for the formation of the myelin sheath that wraps axons a nd is essential to rapid propagation of action potentials in the nervous system. Additionally, an exciting new report has demonstrated that cholesterol is covalently added to the "hedgehog" family of small proteins during a proteolytic maturation process that is required for these proteins to act as important signaling molecules during pattern formation of the developing embryo (Porter et al., 1996). This is an exciting and novel role for the cholesterol molecule.