Ras1 and Ras2 contribute shared and unique roles in physiology and virulence of Cryptococcus neoformans The GenBank accession number for the RAS2 sequence of C. neoformans H99 is AF294349.

Abstract

The Ras1 signal transduction pathway controls the ability of the pathogenic fungus Cryptococcus neoformans to grow at high temperatures and to mate. A second RAS gene was identified in this organism. RAS2 is expressed at a very low level compared to RAS1, and a ras2 mutation caused no alterations in vegetative growth rate, differentiation or virulence factor expression. The ras2 mutant strain was equally virulent to the wild-type strain in the murine inhalational model of cryptococcosis. Although a ras1 ras2 double mutant strain is viable, mutation of both RAS genes results in a decreased growth rate at all temperatures compared to strains with either single mutation. Overexpression of the RAS2 gene completely suppressed the ras1 mutant mating defect and partially suppressed its high temperature growth defect. After prolonged incubation at a restrictive temperature, the ras1 mutant demonstrated actin polarity defects that were also partially suppressed by RAS2 overexpression. These studies indicate that the C. neoformans Ras1 and Ras2 proteins share overlapping functions, but also play distinct signalling roles. Our findings also suggest a mechanism by which Ras1 controls growth of this pathogenic fungus at 37 mC, supporting a conserved role for Ras homologues in microbial cellular differentiation, morphogenesis and virulence.

Elevation of Intracellular cAMP Levels by Dominant Active Heterotrimeric G Protein Alpha SubunitsScGP-AandScGP-Cin Homobasidiomycete,Schizophyllum commune

“…The alignment score between the deduced amino acid sequence and the Ras1p gene submitted by Gorfer is 98% (data not shown), and therefore these genes were considered homologous. However, it remains to be seen whether another RAS gene exists in S. commune as in C. neoformans, 32) and homobasidiomycete Suillus bovinus ras1 and ras2. Since the amino acid sequences of the RAS gene have been well conserved in most species, it might be possible to discover other RAS genes in S. commune by degenerate PCR or substitutional techniques.…”

Basidiomycete Mating Type Genes and Pheromone Signaling

“…In Cr. neoformans, Ras1 expression is higher than Ras2 and the protein functions mainly overlap (114). Interestingly, in Cr.…”

“…The function of Ras proteins encoded by two different genes, Ras1 and Ras2, has been extensively analyzed in S. cerevisiae (108), Cr. neoformans (68,69,114,115,118), and U. maydis (52,64). Several aspects complicate the understanding of the function of Ras proteins, as Ras gene expression is often controlled by nutritional and environmental factors.…”

Regulatory Circuitry Governing Fungal Development, Drug Resistance, and Disease

“…C. neoformans also possesses a Ras2 protein. On their own, ras2 mutants display no obvious phenotypes, although an overexpression of RAS2 is able to partially suppress ras1 mutant phenotypes (619). Additional studies have shown that ras1 mutants are viable but are unable to grow at elevated temperatures, show defects in mating and agar adherence, and are avirulent in rabbit models of cryptococcal meningitis (9).…”