Role of Nrg1 in the regulation of morphogenesis in Candida albicans.
Silvia Argimon, Claire L. Russell, Abigail Mavor, Claire Manson, Susan MacKaskill, Alistair J.P. Brown
Aberdeen Fungal Group, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, United Kingdom
Morphogenetic transitions between yeast and hyphal growth forms are thought to contribute to the virulence of Candida albicans, an opportunistic pathogen of humans. Hyphal development is negatively regulated by Nrg1 and Tup1 [1-3]. Our transcript profiling data has indicated that Nrg1 and Tup1 play global roles in the regulation of several virulence factors in C. albicans. Nrg1 also represses metabolic genes, energy-related functions and genes involved in cell rescue. Using a one-hybrid system, we showed that Nrg1 can act as a transcriptional repressor in C. albicans, operating in a Tup1-dependent fashion. Nrg1 acts via the Nrg1 Response Element (NRE: [A/C][A/C/G]C3T) to repress transcription in C. albicans. Using an NRE-StlacZ reporter, we have revealed that the cAMP pathway plays a key role in the regulation of Nrg1-mediated repression, though the TOR pathway may also modulate the activity of this repressor. This suggests integration of negative and positive morphogenetic signalling pathways in C. albicans. We have also shown that Nrg1 is a phosphoprotein. Nrg1 is phosphorylated in budding cells, and is rapidly and transiently dephosphorylated in response to a hypha-inducing signal. Hence the activity of the sequence-specific DNA binding protein, Nrg1, appears to be regulated at both transcriptional and post-translational levels. 1. Braun & Johnson (1997) Science 277, 105-109. 2. Braun et al. (2001) EMBO. J. 20, 4753-4761. 3. Murad et al. (2001) EMBO. J. 20, 4742-4752.