MANNOLIPID BIOSYNTHESIS, TURNOVER AND TRANSPORT

甘露脂生物合成、周转和运输

• 批准号: 6105353
• 负责人: ALAN Michael TARTAKOFF
• 金额: $ 14.93万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6105353
• 关键词: cerebrohepatorenal syndrome; cinefluorography; dolichol; endoplasmic reticulum; gene expression; gene mutation; glycolipids; guinea pigs; intracellular transport; lipid biosynthesis; lipid metabolism; lipid structure; mannose; messenger RNA; microsomes; pancreas; phosphatidylinositols; thin layer chromatography; tissue /cell culture; transfection; cerebrohepatorenal syndrome; cinefluorography; dolichol; endoplasmic reticulum; gene expression; gene mutation; glycolipids; guinea pigs; intracellular transport; lipid biosynthesis; lipid metabolism; lipid structure; mannose; messenger RNA; microsomes; pancreas; phosphatidylinositols; thin layer chromatography; tissue /cell culture; transfection

The proposed experiments evaluate the biosynthesis, turnover and possible transport of mannose-containing lipids in animal cells and yeast. Certain mannolipids which include phosphatidylinositol (PI) become the membrane anchors of glycosyl phosphatidylinositol (GPI)-anchored proteins. Those which include dolichol contribute their glycans as asparagine-linked glycans of glycoproteins. Experiments will analyze: 1a) the turnover and possible transport of these two classes of mannolipids, 1b) the turnover and possible transport of mannolipids of incomplete structure produced by mutant cells, 2) the ability of mutant cells to internalize polar mannolipids from the cell surface to the RER, thereby correcting GPI-anchoring defects, 3) whether mutant cells which cannot synthesize ether lipids are able to synthesize PI-linked mannolipids or GPI-anchors and the possible significance of any such deficiency in Zellweger's syndrome, 4) whether PI-linked mannolipids can be transferred to protein acceptors when pancreatic microsomes are programmed with mRNA of a protein which normally bears a GPI anchor.

提出的实验评估了生物合成，周转和可能 在动物细胞和酵母中含甘露糖的脂质的转运。 肯定 包括磷脂酰肌醇（PI）的甘露脂蛋白成为膜 糖基磷脂酰肌醇（GPI）锚定蛋白的锚。 那些 其中包括多利果（Dolichol 糖蛋白的聚糖。 实验将分析： 1A）这两类的营业额和运输可能 mannolipids， 1b）不完整的曼诺脂脂的营业额和运输 突变细胞产生的结构， 2）突变细胞内化极性甘露脂素的能力 细胞表面到RER，从而纠正GPI锚定缺陷， 3）是否无法合成醚脂质的突变细胞能够 合成PI连接的Mannolipids或GPI锚定，可能 Zellweger综合征的任何这种缺乏的意义， 4）是否可以将PI连接的甘露脂素转移到蛋白质受体中 当用蛋白质的mRNA对胰腺微粒体进行编程时 通常带有GPI锚。