An Endocytic Mechanism for Haemoglobin-Iron Acquisition in Candida Albicans

Mol Microbiol. 2008 Jul;69(1):201-17. doi: 10.1111/j.1365-2958.2008.06277.x. Epub 2008 May 5.

Abstract

The fungal pathogen Candida albicans is able to utilize haemin and haemoglobin as iron sources. Haem-iron utilization is facilitated by Rbt5, an extracellular, glycosylphophatidylinositol (GPI)-anchored, haemin- and haemoglobin-binding protein. Here, we show that Rbt5 and its close homologue Rbt51 are short-lived plasma membrane proteins, degradation of which depends on vacuolar activity. Rbt5 facilitates the rapid endocytosis of haemoglobin into the C. albicans vacuole. We relied on recapitulation of the Rbt51-dependent haem-iron utilization in Saccharomyces cerevisiae to identify mutants defective in haemoglobin utilization. Homologues of representative mutants in S. cerevisiae were deleted in C. albicans and tested for haemoglobin-iron utilization and haemoglobin uptake. These mutants define a novel endocytosis-mediated haemoglobin utilization mechanism that depends on acidification of the lumen of the late secretory pathway, on a type I myosin and on the activity of the ESCRT pathway.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Candida albicans / chemistry
  • Candida albicans / genetics
  • Candida albicans / metabolism*
  • Endocytosis*
  • Ferrichrome / metabolism
  • Fungal Proteins / analysis
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Hemoglobins / metabolism*
  • Iron / metabolism*
  • Iron-Binding Proteins / analysis
  • Iron-Binding Proteins / genetics
  • Iron-Binding Proteins / metabolism*
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Protein Transport
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Vacuoles / metabolism

Substances

  • Fungal Proteins
  • Hemoglobins
  • Iron-Binding Proteins
  • Membrane Proteins
  • Ferrichrome
  • Iron