MANNOLIPID BIOSYNTHESIS, TURNOVER AND TRANSPORT

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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.