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Journal of Lipid Research, Vol. 48, 993-1011, May 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology
Thematic Review |
Thematic review series: Lipid Posttranslational Modifications. GPI anchoring of protein in yeast and mammalian cells, or: how we learned to stop worrying and love glycophospholipids
* Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801
Department of Biochemistry, Weill Cornell Medical College, New York, NY 10021
Published, JLR Papers in Press, March 14, 2007.
1 To whom correspondence should be addressed. e-mail: p-orlean{at}uiuc.edu (P.O.); akm2003{at}med.cornell.edu (A.K.M.)
Glycosylphosphatidylinositol (GPI) anchoring of cell surface proteins is the most complex and metabolically expensive of the lipid posttranslational modifications described to date. The GPI anchor is synthesized via a membrane-bound multistep pathway in the endoplasmic reticulum (ER) requiring >20 gene products. The pathway is initiated on the cytoplasmic side of the ER and completed in the ER lumen, necessitating flipping of a glycolipid intermediate across the membrane. The completed GPI anchor is attached to proteins that have been translocated across the ER membrane and that display a GPI signal anchor sequence at the C terminus. GPI proteins transit the secretory pathway to the cell surface; in yeast, many become covalently attached to the cell wall. Genes encoding proteins involved in all but one of the predicted steps in the assembly of the GPI precursor glycolipid and its transfer to protein in mammals and yeast have now been identified. Most of these genes encode polytopic membrane proteins, some of which are organized in complexes. The steps in GPI assembly, and the enzymes that carry them out, are highly conserved. GPI biosynthesis is essential for viability in yeast and for embryonic development in mammals. In this review, we describe the biosynthesis of mammalian and yeast GPIs, their transfer to protein, and their subsequent processing.
Supplementary key words glycosyltransferase • flippase • dolichol • phosphatidylethanolamine • phosphatidylinositol • endoplasmic reticulum • cell wall • glycosylphosphatidylinositol
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