A Rac homolog functions downstream of Ras1 to control hyphal differentiation and high-temperature growth in the pathogenic fungus Cryptococcus neoformans.

Published

Journal Article

The Cryptococcus neoformans Ras1 protein serves as a central regulator for several signaling pathways. Ras1 controls the induction of the mating pheromone response cascade as well as a distinct signaling pathway that allows this pathogenic fungus to grow at human physiological temperature. To characterize elements of the Ras1-dependent high-temperature growth pathway, we performed a multicopy suppressor screen, identifying genes whose overexpression allows the ras1 mutant to grow at 37 degrees C. Using this genetic technique, we identified a C. neoformans gene encoding a Rac homolog that suppresses multiple ras1 mutant phenotypes. Deletion of the RAC1 gene does not affect high-temperature growth. However, a rac1 mutant strain demonstrates a profound defect in haploid filamentation as well as attenuated mating. In a yeast two-hybrid assay, Rac1 physically interacts with the PAK kinase Ste20, which similarly regulates hyphal formation in this fungus. Similar to Rac1, overexpression of the STE20alpha gene also restores high-temperature growth to the ras1 mutant. These results support a model in which the small G protein Rac1 acts downstream of Ras proteins and coordinately with Ste20 to control high-temperature growth and cellular differentiation in this human fungal pathogen.

Full Text

Duke Authors

Cited Authors

  • Vallim, MA; Nichols, CB; Fernandes, L; Cramer, KL; Alspaugh, JA

Published Date

  • June 2005

Published In

Volume / Issue

  • 4 / 6

Start / End Page

  • 1066 - 1078

PubMed ID

  • 15947199

Pubmed Central ID

  • 15947199

International Standard Serial Number (ISSN)

  • 1535-9778

Digital Object Identifier (DOI)

  • 10.1128/EC.4.6.1066-1078.2005

Language

  • eng

Conference Location

  • United States