title: Regulation of the transport and protein levels of the inositol phosphorylceramide mannosyltransferases Csg1 and Csh1 by the Ca2+-binding protein Csg2.
abstract: Complex sphingolipids in yeast are known to function in cellular adaptation to environmental changes. One of the yeast complex sphingolipids, mannosylinositol phosphorylceramide (MIPC), is produced by the redundant inositol phosphorylceramide (IPC) mannosyltransferases Csg1 and Csh1. The Ca2+-binding protein Csg2 can form a complex with either Csg1 or Csh1 and is considered to act as a regulatory subunit. However, the role of Csg2 in MIPC synthesis has remained unclear. In this study, we found that Csg1 and Csh1 are N-glycosylated with core-type and mannan-type structures, respectively. Further identification of the glycosylated residues suggests that both Csg1 and Csh1 exhibit membrane topology with their C termini in the cytosol and their mannosyltransferase domains in the lumen. After complexing with Csg2, both Csg1 and Csh1 function in the Golgi, and then are delivered to the vacuole for degradation. However, uncomplexed Csh1 cannot exit from the endoplasmic reticulum. We also demonstrated that Ca2+ stimulates IPC-to-MIPC conversion, because of a Csg2-dependent increase in Csg1 levels. Thus, Csg2 has several regulatory functions for Csg1 and Csh1, including stability, transport, and gene expression.
authors.affiliation: Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, 4-4-1, Komatsushima, Sendai, Miyagi 981-8558, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uemura
authors.forename: Akio
authors.initials: A
authors.lastname: Kihara
authors.forename: Soichiro
authors.initials: S
authors.lastname: Iwaki
authors.forename: Jin-ichi
authors.initials: J
authors.lastname: Inokuchi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Igarashi
mesh_terms: D002135:Calcium-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D006031:Glycosylation; D016695:Glycosyltransferases; D006056:Golgi Apparatus / Q000378:metabolism; D008364:Mannosyltransferases / Q000737:chemistry* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D011134:Polysaccharides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012097:Repressor Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013395:Sucrose / Q000737:chemistry
chemical_list: C086192:CSG2 protein, S cerevisiae; D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; D011134:Polysaccharides; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D013395:Sucrose; D016695:Glycosyltransferases; C092031:SUR1 protein, S cerevisiae; C519168:Csh1 protein, S cerevisiae; D008364:Mannosyltransferases