Phospholipase D Regulation of Exosome Secretion

磷脂酶 D 对外泌体分泌的调节

• 批准号: 2325227
• 负责人: Michelle Knowles
• 金额: $ 63.95万
• 依托单位: University of Denver
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2325227&HistoricalAwards=false
• 关键词: Phospholipase; Regulation; Exosome; Secretion

With the support of the Chemistry of Life Processes Program in the Division of Chemistry, Michelle Knowles of the University of Denver is studying how cells control their communication with one another. One way that cells communicate is through the secretion of nanoscopic packets called “exosomes.” Exosomes are lipid-coated containers that carry molecules and travel through the body, where they are taken up by other cells. Exosomes can alter the function of other cells, for better or worse. The factors that control how cells make exosomes and their release are not fully understood. The research supported by this award will focus on the lipid-modifying protein, phospholipase D (PLD), an enzyme, and on phosphatidic acid (PA), which is a lipid whose production is catalyzed by PLD. PA can alter the shapes of membranes and acts as a signaling molecule. The role of PLD and PA in the formation of exosomes and their release will be investigated. Beyond generating new knowledge about exosomes, the project will create opportunities for graduate and undergraduate students to learn how to use state of the art technology to address problems at the forefront of cell communication. Drs. Knowles and Dinah Loerke (University of Denver) will develop a peer mentoring program for graduate students. The results of scientific and broader impact activities will be presented at conferences and published to allow others to build upon the foundational knowledge obtained about cellular regulation and student mentorship.Phospholipase D and phospholipase A (PLD and PA) could be involved in the formation of exosomes and/or in the release process itself. Both steps require highly curved membranes. In this research project, the presence of PLD and the formation of PA will be mapped in space and time during exosome secretion. Quantitative fluorescence microscopy approaches will be used in conjunction with standard biochemical methods to assess the number of exosomes and the frequency with which they are released from cells. The formation, trafficking and fusion stages of the exosome lifecycle will be assessed in live cells. The activity and presence of PLD will be altered to determine when and where PLD and phosphatidic acid are required. This project has the potential for far-reaching scientific impact; specifically, by demonstrating the use of biophysical tools/chemical biology to help to elucidate important mechanisms of cellular communication.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学划分的化学方面，米歇尔（Michelle）对丹佛（Els）的沟通良好。无论好坏膜的形状与信号分子一样。在细胞交流的最前沿的地址问题。脂肪酶D和磷脂酶A（PLD和PA）可能参与外泌体的形成和/或在这两个步骤中都需要高度弯曲的膜。在外部体内将在空间和时间上进行映射。 。和更广泛的影响审查标准。