Physicochemical foundations of lipid phosphomonoester group mediated cell signaling events

点击翻译按钮获取中文摘要

The extraordinary chemical diversity of lipids provides the foundation for the many roles they fulfill in cellular systems, which ranges from controlling the structural and morpho¬logical properties of cell membranes to mediating crucial cell signaling events. Lipids with phosphate groups are ideally suited to affect protein functions and they have been shown to control an ever-increasing array of cell signaling events. The selective binding of proteins to lipid molecules with phosphate groups like phosphoinositides, ceramide-1-phosphate, sphingosine-1-phosphate or phosphatidic acid provides the specificity of the signaling event. Kinases and phosphatases, which upon activation alter the number of phosphate groups attached to the lipid headgroup, provide the temporal control, while the spatial control is rooted in the rich chemical functionality of the respective headgroup that gives rise to local enrichment through interactions with other membrane resident molecules. Despite the importance for lipid signaling, lipids with phosphate groups in their headgroup have not been identified as a unit with a common theme and their properties have not been investigated in a comparative manner. The experiments outlined by the PIs are designed to identify the physico¬chemical commonalities these lipid signaling molecules exhibit, while at the same time they are designed to highlight the disparities among these lipids that give rise to their selective protein binding, differences in lateral distribution and their varying subcellular localization. The PIs will investigate the extent and consequences of hydrogen bond formation between like and unlike lipid species with phosphate groups, the effect of cholesterol on the lateral distribution of these lipids species, the interaction of these lipids with arginine, lysine and histidine amino acid residues and the impact of lipid morphology on the activity of lipid modifying enzymes. The PIs will continue their partnership with the Max Planck Institute (MPI) for Colloids and Interfaces (Germany). One undergraduate student each summer will visit the MPI for a 10 week inter¬national research experience that exposes the student to a different cultural environ¬ment and at the same time allows the student to work at a premier research institution. During the academic year undergraduate students will work in the PIs research labs, which will prepare them for their summer research experience. As in the past, the PIs will strive to identify students from groups underrepresented in the sciences for these experiences.