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Eukaryotic Cell, December 2008, p. 2069-2077, Vol. 7, No. 12
1535-9778/08/$08.00+0     doi:10.1128/EC.00189-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

UGE1 and UGE2 Regulate the UDP-Glucose/UDP-Galactose Equilibrium in Cryptococcus neoformans{triangledown} ,{dagger}

Frédérique Moyrand,1 Ingrid Lafontaine,2 Thierry Fontaine,3 and Guilhem Janbon1*

Institut Pasteur, Unité de Mycologie Moléculaire, CNRS, URA3012, F-75015, France,1 Institut Pasteur, Unité de Génétique Moléculaire des Levures, F-75015, France,2 Institut Pasteur, Unité des Aspergillus, F-75015, France3

Received 12 June 2008/ Accepted 19 September 2008

The genome of the basidiomycete pathogenic yeast Cryptococcus neoformans carries two UDP-glucose epimerase genes (UGE1 and UGE2). UGE2 maps within a galactose cluster composed of a galactokinase homologue gene and a galactose-1-phosphate uridylyltransferase. This clustered organization of the GAL genes is similar to that in most of the hemiascomycete yeast genomes and in Schizosaccharomyces pombe but is otherwise not generally conserved in the fungal kingdom. UGE1 has been identified as necessary for galactoxylomannan biosynthesis and virulence. Here, we show that UGE2 is necessary for C. neoformans cells to utilize galactose as a carbon source at 30°C but is not required for virulence. In contrast, deletion of UGE1 does not affect cell growth on galactose at this temperature. At 37°C, a uge2{Delta} mutant grows on galactose in a UGE1-dependent manner. This compensation by UGE1 of UGE2 mutation for growth on galactose at 37°C was not associated with upregulation of UGE1 transcription or with an increase of the affinity of the enzyme for UDP-galactose at this temperature. We studied the subcellular localization of the two enzymes. Whereas at 30°C, Uge1p is at least partially associated with intracellular vesicles and Uge2p is on the plasma membrane, in cells growing on galactose at 37°C, Uge1p colocalizes with Uge2p to the plasma membrane, suggesting that its activity is regulated through subcellular localization.

* Corresponding author. Mailing address: Unité de Mycologie Moléculaire, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France. Phone: (33) 1 45688356. Fax: (33) 1 45688420. E-mail: janbon{at}pasteur.fr

{triangledown} Published ahead of print on 26 September 2008.

{dagger} Supplemental material for this article may be found at http://ec.asm.org/.

Eukaryotic Cell, December 2008, p. 2069-2077, Vol. 7, No. 12
1535-9778/08/$08.00+0     doi:10.1128/EC.00189-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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