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Glycosylphosphatidylinositol anchors regulate glycosphingolipid levels.

Journal of lipid research (2012-05-26)
Ursula Loizides-Mangold, Fabrice P A David, Victor J Nesatyy, Taroh Kinoshita, Howard Riezman
ABSTRACT

Glycosylphosphatidylinositol (GPI) anchor biosynthesis takes place in the endoplasmic reticulum (ER). After protein attachment, the GPI anchor is transported to the Golgi where it undergoes fatty acid remodeling. The ER exit of GPI-anchored proteins is controlled by glycan remodeling and p24 complexes act as cargo receptors for GPI anchor sorting into COPII vesicles. In this study, we have characterized the lipid profile of mammalian cell lines that have a defect in GPI anchor biosynthesis. Depending on which step of GPI anchor biosynthesis the cells were defective, we observed sphingolipid changes predominantly for very long chain monoglycosylated ceramides (HexCer). We found that the structure of the GPI anchor plays an important role in the control of HexCer levels. GPI anchor-deficient cells that generate short truncated GPI anchor intermediates showed a decrease in very long chain HexCer levels. Cells that synthesize GPI anchors but have a defect in GPI anchor remodeling in the ER have a general increase in HexCer levels. GPI-transamidase-deficient cells that produce no GPI-anchored proteins but generate complete free GPI anchors had unchanged levels of HexCer. In contrast, sphingomyelin levels were mostly unaffected. We therefore propose a model in which the transport of very long chain ceramide from the ER to Golgi is regulated by the transport of GPI anchor molecules.

MATERIALS
Product Number
Brand
Product Description

Avanti
12:0 SM (d18:1/12:0), Avanti Research - A Croda Brand 860583P, powder
Avanti
C17 Ceramide (d18:1/17:0), Avanti Research - A Croda Brand
Avanti
17:0-14:1 PS, Avanti Research - A Croda Brand LM1304, methanol solution
Avanti
C8 Glucosyl(β) Ceramide (d18:1/8:0), Avanti Research - A Croda Brand 860540P, powder
Avanti
12:0 PC (DLPC), 1,2-dilauroyl-sn-glycero-3-phosphocholine, chloroform
Avanti
12:0 PC (DLPC), Avanti Research - A Croda Brand
Avanti
17:0-14:1 PE, Avanti Research - A Croda Brand