9600876 Hasson Caveolae, or "little caves," are flask-shaped invaginations of the plasma membrane that have been observed by electron microscopy in many mammalian cell types. They have been postulated to mediate several cellular processes, including transport across cells (transcytosis), uptake of small molecules (potocytosis), and most recently, transmembrane signal transduction. The caveola is now viewed increasingly as an organelle that plays a critical role in the organization of communication within cells. The long-term goal of this project is the elucidation of the structure and function of caveolae through crystallographic and genetic studies of one of its protein components, caveolin. During the preliminary stage of the project, to be funded by this Research Planning Grant, efforts will be concentrated on obtaining diffraction-quality crystals of a soluble domain of caveolin that mediates oligomerization and interaction with G. %%% In order for a complex organism (such as a human being) to exist, the cells that make it up must be able to communicate with each other. Each cell must be capable of receiving instructions from its environment. A cell receives many kinds of messages and must choose between many possible complex responses. We are trying to understand how a normal cell responds quickly and correctly to each message it receives. It seems that many of the messages transmitted from outside to inside a cell are organized by caveolae, "little caves" on the surface of cells. Caveolae seem to act like telephone switchboards, ensuring that each message is received immediately by the correct protein target inside the cell. Using the technique of X-ray crystallography, we are attempting to determine the structure of the protein caveolin, one of the main components of caveolae, in order to better understand how these switchboards operate. ***
