Ras1 Acts through Duplicated Cdc42 and Rac Proteins to Regulate Morphogenesis and Pathogenesis in the Human Fungal Pathogen Cryptococcus neoformans

• DOI: 10.1371/journal.pgen.1003687
• Publication Date: 2013-08-08T20:52:27Z
• Authors: Elizabeth Ripley ...; Lukasz Kozubowski; Connie B. Nichols; J. Andrew Alspaugh
• Keywords: CDC42; Septin; Rac GTP-Binding Proteins; Fungal protein

Proliferation and morphogenesis in eukaryotic cells depend on the concerted activity of Rho-type GTPases, including Ras, Cdc42, Rac. The sexually dimorphic fungus Cryptococcus neoformans, which encodes paralogous, non-essential copies all three, provides a unique model to examine interactions these conserved proteins. Previously, we demonstrated that RAS1 mediates C. neoformans virulence by acting as central regulator both thermotolerance mating. We report here ras1Δ mutants accumulate defects polarized growth, cytokinesis, cell cycle progression. demonstrate mating can be largely explained compromised four downstream Rho-GTPases: Cdc42 paralogs, Cdc420; Rac Rac1 Rac2. Further, separate GTPase classes play distinct Ras-dependent roles pathogenesis. paralogs primarily control septin localization while primary role growth. Together, duplicate, related signaling proteins provide robust system allow microbial proliferation presence host-derived stresses.