title: An endocytic mechanism for haemoglobin-iron acquisition in Candida albicans.
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.
authors.affiliation: Department of Molecular Microbiology, Technion-B. Rappaport Faculty of Medicine, and the Rappaport Institute for Research in the Medical Sciences, Haifa 31096, Israel.
authors.forename: Ziva
authors.initials: Z
authors.lastname: Weissman
authors.forename: Revital
authors.initials: R
authors.lastname: Shemer
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Conibear
authors.forename: Daniel
authors.initials: D
authors.lastname: Kornitzer
mesh_terms: D002176:Candida albicans / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D005291:Ferrichrome / Q000378:metabolism; D005656:Fungal Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D006454:Hemoglobins; D033862:Iron-Binding Proteins; D008565:Membrane Proteins; D005291:Ferrichrome; D007501:Iron