Molecular Regulation and Transport of Sterols in Plants

Plant sterols represent a complex array of chemical compounds that are essential for many facets of plant growth and development, and are of considerable importance for their nutritional contributions to animals and man. Hence, it is not surprising that the biochemistry and molecular biology of the sterol biosynthetic pathway has been intensively studied. Nonetheless, very little is actually known about the regulation of this biochemical pathway in plants. One goal of our long-term research in sterol metabolism has been focussed on the regulation of squalene synthase, a key enzyme in sterol biosynthetic enzyme. Our recent results suggest that squalene synthase gene expression and enzyme activity are localized to shoot meristems. In attempting to reconcile these results with those already reported in the literature, the most logical interpretation is that sterol biosynthesis itself is localized to this tissue. This interpretation implies that regulation of sterol biosynthesis occurs in the shoot meristem, a tissue that has not been evaluated as such before, and that a sterol transport system for the movement of sterol from the apical meristem throughout the plant must exist. Experiments to test these predictions are proposed and include: 1, an evaluation if sterol biosynthesis localized to the shoot meristem is regulated; 2, the development of a test for long distance transport of sterol within plants; and 3, a determination if NPC1, a highly conserved protein involved in cholesterol uptake and intracellular trafficking, plays a similar role in plants as in animals. The proposed work, which will involve undergraduate and graduate students and a postdoctoral associate, should provide important insights into how this pathway might be engineered for enhanced value using emerging technologies.