» Articles » PMID: 17761529

Saccharomyces Cerevisiae CWH43 is Involved in the Remodeling of the Lipid Moiety of GPI Anchors to Ceramides

Overview
Journal Mol Biol Cell
Date 2007 Sep 1
PMID 17761529
Citations 29
Authors
Affiliations
Soon will be listed here.
Abstract

The glycosylphosphatidylinositol (GPI)-anchored proteins are subjected to lipid remodeling during their biosynthesis. In the yeast Saccharomyces cerevisiae, the mature GPI-anchored proteins contain mainly ceramide or diacylglycerol with a saturated long-fatty acid, whereas conventional phosphatidylinositol (PI) used for GPI biosynthesis contains an unsaturated fatty acid. Here, we report that S. cerevisiae Cwh43p, whose N-terminal region contains a sequence homologous to mammalian PGAP2, is involved in the remodeling of the lipid moiety of GPI anchors to ceramides. In cwh43 disruptant cells, the PI moiety of the GPI-anchored protein contains a saturated long fatty acid and lyso-PI but not inositolphosphorylceramides, which are the main lipid moieties of GPI-anchored proteins from wild-type cells. Moreover, the C-terminal region of Cwh43p (Cwh43-C), which is not present in PGAP2, is essential for the ability to remodel GPI lipids to ceramides. The N-terminal region of Cwh43p (Cwh43-N) is associated with Cwh43-C, and it enhanced the lipid remodeling to ceramides by Cwh43-C. Our results also indicate that mouse FRAG1 and C130090K23, which are homologous to Cwh43-N and -C, respectively, share these activities.

Citing Articles

Structure and Function of the Glycosylphosphatidylinositol Transamidase, a Transmembrane Complex Catalyzing GPI Anchoring of Proteins.

Li D Subcell Biochem. 2024; 104:425-458.

PMID: 38963495 DOI: 10.1007/978-3-031-58843-3_16.


To each its own: Mechanisms of cross-talk between GPI biosynthesis and cAMP-PKA signaling in Candida albicans versus Saccharomyces cerevisiae.

Komath S J Biol Chem. 2024; 300(7):107444.

PMID: 38838772 PMC: 11294708. DOI: 10.1016/j.jbc.2024.107444.


CWH43 Is a Novel Tumor Suppressor Gene with Negative Regulation of TTK in Colorectal Cancer.

Lee C, Tsai K, Lee A, Wei P, Huang C, Batzorig U Int J Mol Sci. 2023; 24(20).

PMID: 37894942 PMC: 10607595. DOI: 10.3390/ijms242015262.


(Patho)Physiology of Glycosylphosphatidylinositol-Anchored Proteins I: Localization at Plasma Membranes and Extracellular Compartments.

Muller G, Muller T Biomolecules. 2023; 13(5).

PMID: 37238725 PMC: 10216265. DOI: 10.3390/biom13050855.


Characterization of Post-Glycosylphosphatidylinositol Attachment to Proteins Phospholipase 3 Like Genes.

Bernat-Silvestre C, Ma Y, Johnson K, Ferrando A, Aniento F, Marcote M Front Plant Sci. 2022; 13:817915.

PMID: 35222477 PMC: 8874281. DOI: 10.3389/fpls.2022.817915.


References
1.
Ferguson M, BRIMACOMBE J, Brown J, Crossman A, Dix A, Field R . The GPI biosynthetic pathway as a therapeutic target for African sleeping sickness. Biochim Biophys Acta. 1999; 1455(2-3):327-40. DOI: 10.1016/s0925-4439(99)00058-7. View

2.
Okamoto M, Yoko-O T, Umemura M, Nakayama K, Jigami Y . Glycosylphosphatidylinositol-anchored proteins are required for the transport of detergent-resistant microdomain-associated membrane proteins Tat2p and Fur4p. J Biol Chem. 2005; 281(7):4013-23. DOI: 10.1074/jbc.M504684200. View

3.
Oxley D, Bacic A . Structure of the glycosylphosphatidylinositol anchor of an arabinogalactan protein from Pyrus communis suspension-cultured cells. Proc Natl Acad Sci U S A. 1999; 96(25):14246-51. PMC: 24422. DOI: 10.1073/pnas.96.25.14246. View

4.
Bagnat M, Keranen S, Shevchenko A, Simons K . Lipid rafts function in biosynthetic delivery of proteins to the cell surface in yeast. Proc Natl Acad Sci U S A. 2000; 97(7):3254-9. PMC: 16225. DOI: 10.1073/pnas.97.7.3254. View

5.
Guillas I, Pfefferli M, Conzelmann A . Analysis of ceramides present in glycosylphosphatidylinositol anchored proteins of Saccharomyces cerevisiae. Methods Enzymol. 2000; 312:506-15. DOI: 10.1016/s0076-6879(00)12935-0. View