FLUORESCENT ANALYSIS OF REGULATION OF CHOLESTEROL METABOLISM IN MAMMALIAN CELL

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。我们研究项目的主要重点是了解高等动物的胆固醇代谢是如何调节的。胆固醇是几乎所有哺乳动物细胞质膜的主要结构分子。其独特的化学和几何特性使其在膜功能中发挥理想作用，因为它提供了结构刚性并有助于脂质双分子层的选择性渗透。此外，胆固醇在更特殊的生物过程中起着重要作用。它是极低密度脂蛋白颗粒的主要成分，由肝脏分泌，用于将胆固醇和甘油三酯运送到身体的其他部位；胆固醇是合成类固醇激素和胆汁酸所需的前体，而这些激素和胆汁酸是适当的营养、生长和发育所必需的。此外，胆固醇分子优良的绝缘能力被用来形成包裹轴突的髓鞘，这对神经系统中动作电位的快速传播至关重要。此外，一项令人兴奋的新报告表明，在蛋白质水解成熟过程中，胆固醇被共价添加到“刺猬”小蛋白家族中，这是这些蛋白质在发育中的胚胎模式形成过程中作为重要信号分子所必需的（Porter等人，1996）。这对胆固醇分子来说是一个令人兴奋的新角色。

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.