The catalytic subunit of the first mannosyltransferase in the GPI biosynthetic pathway affects growth, cell wall integrity and hyphal morphogenesis in Candida albicans

Yeast. 2016 Aug;33(8):365-83. doi: 10.1002/yea.3179.

Abstract

CaGpi14 is the catalytic subunit of the first mannosyltransferase that is involved in the glycosylphosphatidylinositol (GPI) biosynthetic pathway in Candida albicans. We show that CaGPI14 is able to rescue a conditionally lethal gpi14 mutant of Saccharomyces cerevisiae, unlike its mammalian homologue. The depletion of this enzyme in C. albicans leads to severe growth defects, besides causing deficiencies in GPI anchor levels. In addition, CaGpi14 depletion results in cell wall defects and upregulation of the cell wall integrity response pathway. This in turn appears to trigger the osmotic-stress dependent activation of the HOG1 pathway and an upregulation of HOG1 as well as its downstream target, SKO1, a known suppressor of expression of hyphae-specific genes. Consistent with this, mutants of CaGPI14 are unable to undergo hyphal transformations in different hyphae-inducing media, under conditions that produce abundant hyphae in the wild-type cells. Hyphal defects in the CaGPI14 mutants could not be attributed either to reduced protein kinase C activation or to defective Ras signalling in these cells but appeared to be driven by perturbations in the HOG1 pathway. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: C. albicans; GPI anchor; HOG1 pathway; cell wall defects; hyphal morphogenesis; mannosyltransferase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic-Leucine Zipper Transcription Factors / genetics
  • Candida albicans / enzymology
  • Candida albicans / genetics
  • Candida albicans / growth & development*
  • Catalytic Domain*
  • Cell Wall / metabolism*
  • Genes, Lethal
  • Glycosylphosphatidylinositols / biosynthesis*
  • Hyphae / enzymology
  • Hyphae / genetics
  • Hyphae / growth & development*
  • Mannosyltransferases / chemistry
  • Mannosyltransferases / genetics
  • Mannosyltransferases / metabolism*
  • Mitogen-Activated Protein Kinases / genetics
  • Morphogenesis
  • Mutation
  • Osmotic Pressure
  • Protein Kinase C / metabolism
  • Repressor Proteins / genetics
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • Basic-Leucine Zipper Transcription Factors
  • Glycosylphosphatidylinositols
  • Repressor Proteins
  • SKO1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Mannosyltransferases
  • Protein Kinase C
  • HOG1 protein, S cerevisiae
  • Mitogen-Activated Protein Kinases