Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
5P01DK038181-08
Application #
3754357
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Case Western Reserve University
Department
Type
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106

  Publications

Chen, R; Knez, J J; Merrick, W C et al. (2001) Comparative efficiencies of C-terminal signals of native glycophosphatidylinositol (GPI)-anchored proproteins in conferring GPI-anchoring. J Cell Biochem 84:68-83
Wongkajornsilp, A; Sevlever, D; Rosenberry, T L (2001) Metabolism of exogenous sn-1-alkyl-sn-2-lyso-glucosaminyl-phosphatidylinositol in HeLa D cells: accumulation of glucosaminyl(acyl)phosphatidylinositol in a metabolically inert compartment. Biochem J 359:305-13
Premkumar, D R; Fukuoka, Y; Sevlever, D et al. (2001) Properties of exogenously added GPI-anchored proteins following their incorporation into cells. J Cell Biochem 82:234-45
Sevlever, D; Pickett, S; Mann, K J et al. (1999) Glycosylphosphatidylinositol-anchor intermediates associate with triton-insoluble membranes in subcellular compartments that include the endoplasmic reticulum. Biochem J 343 Pt 3:627-35
Chen, A; Meyerson, H J; Salvekar, A et al. (1998) Non-glycosylated human B7-1(CD80) retains the capacity to bind its counter-receptors. FEBS Lett 428:127-34
Chen, R; Walter, E I; Parker, G et al. (1998) Mammalian glycophosphatidylinositol anchor transfer to proteins and posttransfer deacylation. Proc Natl Acad Sci U S A 95:9512-7
Kraus, D; Medof, M E; Mold, C (1998) Complementary recognition of alternative pathway activators by decay-accelerating factor and factor H. Infect Immun 66:399-405
Sevlever, D; Schiemann, D; Guidubaldi, J et al. (1997) Accumulation of glucosaminyl(acyl)phosphatidylinositol in an S3 HeLa subline expressing normal dolicholphosphomannose synthase activity. Biochem J 321 ( Pt 3):837-44
Yu, J; Nagarajan, S; Knez, J J et al. (1997) The affected gene underlying the class K glycosylphosphatidylinositol (GPI) surface protein defect codes for the GPI transamidase. Proc Natl Acad Sci U S A 94:12580-5
Meyerson, H J; Huang, J H; Fayen, J D et al. (1996) Functional dissociation of CD8 alpha's Ig homologue and connecting peptide domains. J Immunol 156:574-84

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