Surface Potentials and Second Messengers

本项目的目标是研究生产第二信使时的静电势。磷脂酰肌醇4，5-二磷酸(PIP2)是一种存在于细胞膜表面的脂质，它的水解会产生1，4，5-三磷酸肌醇(IP3)和二酰甘油(DG)。IP3诱导钙的释放；DG激活蛋白激酶C；McLaughlin博士将开展一系列项目，包括：1)研究新霉素等多价阳离子与PIP2的结合；2)标记PIP2的碳氢尾并进行荧光能量转移测量；3)研究静电势对钙激活聚磷肌醇特异性磷脂酶C能力的影响；4)继续理论和实验研究表面电位和协作性在双层膜中多价阳离子与单价阴离子脂结合中的作用。虽然很少有生物物理学家在这一领域工作，关于影响这些第二信使的产生和作用机制的物理因素的信息也很少，但有大量证据表明，这些因素之一是由磷脂酰丝氨酸等带电脂质产生的静电势。

The objective of this project is to examine the electrostatic potentials on the production of second messengers. The hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a lipid located on the cytoplasmic surface of cell membranes, produces inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DG). IP3 induces the release of calcium; DG activates a protein kinase C. Dr. McLaughlin will carry out a number of projects including: 1) studying the binding of polyvalent cations like neomycin to PIP2; 2) labelling the hydrocarbon tails of PIP2 and making fluorescence energy transfer measurements; 3) studying the effect of electrostatic potentials on the ability of calcium to activate a polyphosphoinositide-specific phospholipase C; and 4) continuing theoretical and experimental studies of the role of surface potentials and cooperativity in the binding of polyvalent cations to monovalent anionic lipids in bilayer membranes. Although very few biophysicists are working in this area and little information is available about the physical factors that influence the production and mechanism of action of these second messengers, there is a great deal of evidence present for believing that one of these factors is the electrostatic potential produced by charged lipids such as phosphatidylserine.