title: Cdc1 removes the ethanolamine phosphate of the first mannose of GPI anchors and thereby facilitates the integration of GPI proteins into the yeast cell wall.
abstract: Temperature-sensitive cdc1(ts) mutants are reported to stop the cell cycle upon a shift to 30°C in early G2, that is, as small budded cells having completed DNA replication but unable to duplicate the spindle pole body. A recent report showed that PGAP5, a human homologue of CDC1, acts as a phosphodiesterase removing an ethanolamine phosphate (EtN-P) from mannose 2 of the glycosylphosphatidylinositol (GPI) anchor, thus permitting efficient endoplasmic reticulum (ER)-to-Golgi transport of GPI proteins. We find that the essential CDC1 gene can be deleted in mcd4∆ cells, which do not attach EtN-P to mannose 1 of the GPI anchor, suggesting that Cdc1 removes the EtN-P added by Mcd4. Cdc1-314(ts) mutants do not accumulate GPI proteins in the ER but have a partial secretion block later in the secretory pathway. Growth tests and the genetic interaction profile of cdc1-314(ts) pinpoint a distinct cell wall defect. Osmotic support restores GPI protein secretion and actin polarization but not growth. Cell walls of cdc1-314(ts) mutants contain large amounts of GPI proteins that are easily released by β-glucanases and not attached to cell wall β1,6-glucans and that retain their original GPI anchor lipid. This suggests that the presumed transglycosidases Dfg5 and Dcw1 of cdc1-314(ts) transfer GPI proteins to cell wall β1,6-glucans inefficiently.
authors.affiliation: Department of Biology, University of Fribourg, CH-1700 Fribourg, Switzerland.
authors.forename: Hector M
authors.initials: HM
authors.lastname: Vazquez
authors.affiliation: Department of Biology, University of Fribourg, CH-1700 Fribourg, Switzerland.
authors.forename: Christine
authors.initials: C
authors.lastname: Vionnet
authors.affiliation: Department of Biology, University of Fribourg, CH-1700 Fribourg, Switzerland.
authors.forename: Carole
authors.initials: C
authors.lastname: Roubaty
authors.affiliation: Department of Biology, University of Fribourg, CH-1700 Fribourg, Switzerland andreas.conzelmann@unifr.ch.
authors.forename: Andreas
authors.initials: A
authors.lastname: Conzelmann
mesh_terms: D000199:Actins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002473:Cell Wall / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004983:Ethanolamines / Q000378:metabolism; D005936:Glucans / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000378:metabolism*; D008358:Mannose / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D021381:Protein Transport / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013012:Sorbitol / Q000494:pharmacology
chemical_list: D000199:Actins; C090459:CDC1 protein, S cerevisiae; C093810:CWP1 protein, S cerevisiae; C093811:CWP2 protein, S cerevisiae; D018797:Cell Cycle Proteins; D004983:Ethanolamines; D005936:Glucans; D017261:Glycosylphosphatidylinositols; C118052:MCD4 protein, S cerevisiae; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D013012:Sorbitol; C005448:phosphorylethanolamine; D008358:Mannose