Physicochemical foundations of lipid phosphomonoester group mediated cell signaling events

脂类特殊的化学多样性为它们在细胞系统中发挥的许多作用提供了基础，这些作用范围从控制细胞膜的结构和形态属性到调节关键的细胞信号事件。带有磷酸基团的脂类非常适合影响蛋白质的功能，它们已被证明控制着一系列不断增加的细胞信号事件。磷脂酰肌醇、神经酰胺-1-磷酸、鞘氨醇-1-磷酸或磷脂酸等磷酸基团选择性地将蛋白质与脂分子结合，提供了信号事件的特异性。激酶和磷酸酶在激活后改变附着在脂头基团上的磷酸基团的数量，提供时间控制，而空间控制植根于各自头基的丰富化学功能，通过与其他膜驻留分子的相互作用引起局部浓缩。尽管脂质信号的重要性，但其头基团中含有磷酸基团的脂类尚未被确定为具有共同主题的单位，其性质也没有以比较的方式进行研究。PI概述的实验旨在确定这些脂质信号分子表现出的物理化学共性，同时它们也旨在突出这些脂类之间的差异，这些差异导致它们选择性结合蛋白质，横向分布的差异以及它们不同的亚细胞定位。PIS将调查类似和不同类脂物种与磷酸盐基团之间形成氢键的程度和后果，胆固醇对这些类脂物种横向分布的影响，这些类脂与精氨酸、赖氨酸和组氨酸氨基酸残基的相互作用，以及类脂形态对脂类修饰酶活性的影响。PIS将继续与马克斯·普朗克胶体和界面研究所(MPI)(德国)合作。每年夏天，一名本科生将访问MPI，进行为期10周的国际研究体验，让学生接触到不同的文化环境，同时允许学生在一流的研究机构工作。在学年期间，本科生将在PIS研究实验室工作，这将为他们的暑期研究经历做好准备。一如既往，专业督学将致力于从科学界代表性不足的群体中寻找这些经历的学生。

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.