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

An endocytic mechanism for haemoglobin-iron acquisition in Candida albicans.

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Department of Molecular Microbiology, Technion-B. Rappaport Faculty of Medicine, and the Rappaport Institute for Research in the Medical Sciences, Haifa 31096, Israel.


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.

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