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

Mol Biol Cell. 2014 Nov 1;25(21):3375-88. doi: 10.1091/mbc.E14-06-1033. Epub 2014 Aug 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Wall / genetics
  • Cell Wall / metabolism*
  • Endoplasmic Reticulum / metabolism
  • Ethanolamines / metabolism
  • Glucans / metabolism
  • Glycosylphosphatidylinositols / chemistry
  • Glycosylphosphatidylinositols / metabolism*
  • Mannose / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mutation
  • Protein Transport / drug effects
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sorbitol / pharmacology

Substances

  • Actins
  • CDC1 protein, S cerevisiae
  • CWP1 protein, S cerevisiae
  • CWP2 protein, S cerevisiae
  • Cell Cycle Proteins
  • Ethanolamines
  • Glucans
  • Glycosylphosphatidylinositols
  • MCD4 protein, S cerevisiae
  • Membrane Glycoproteins
  • Membrane Proteins
  • Saccharomyces cerevisiae Proteins
  • Sorbitol
  • phosphorylethanolamine
  • Mannose