Multifunctional roles of glycosyl-phosphatidylinositol lipids

The results presented here indicate that GPI lipids are a structurally and functionally diverse molecular family. Despite new detailed information on the structures of GPI-anchored proteins, there is relatively scant information on the structure of free-GPI. Thus, little is known of the relationships between GPI structures and the mechanism of their biological effects. For example, there is no distinction at the structural level between hormone-sensitive free-GPI and those that serve as precursors for protein-GPI. Nor is there precise biochemical data on the mechanism and importance of free-GPI in hormone signaling, or the signaling roles that GPI anchors play in protein function. The T-cell activation cascade is an ideal system for studying both forms of GPI and their derivatives. The study of GPI molecules in T lymphocytes offers the exciting possibility of addressing questions on the structure, function, genesis, and regulation of both free- and protein-GPI molecules in a single cell type. The detection of multiple protein-GPI and free-GPI forms, and of hormone-sensitive GPI, provides the first approach to these issues. For the moment, the potential for biochemical signaling by intact GPI or its metabolites is enormous. If significant progress is to be made, the structures of hormone sensitive free-GPI must be elucidated. Only then can we precisely define the roles of these molecules in the regulation of cell metabolism and proliferation.