Ras-Mediated Signaling in Pathogenic Fungi

Ras proteins are small GTPases that function as molecular switches governing growth, morphogenesis and stress responses in eukaryotic organisms. In pathogenic fungi, Ras-mediated signalling integrates external cues—such as nutrient availability, pH and host-derived signals—with intracellular cascades that control hyphal extension, spore formation and biofilm development. Activation of Ras requires exchange of GDP for GTP, followed by precise post-translational modifications that direct Ras to the plasma membrane. Once membrane-bound, Ras interacts with key effectors including adenylate cyclase, mitogen-activated protein kinases and Rho GTPases to regulate cytoskeletal organisation, cell wall biosynthesis and secretion of virulence factors. Disruption of any step in this pathway often leads to attenuated pathogenicity, making components of the Ras network attractive targets for novel antifungal therapies. Recent advances have elucidated fungal-specific domains and regulatory mechanisms that distinguish pathogen Ras signalling from that in mammalian hosts, offering routes to selective intervention.

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Ras-Mediated Signaling in Pathogenic Fungi publication trend

The graph below shows the total number of articles in ras-mediated signaling in pathogenic fungi across all publications each year (not limited to Nature Index journals).

Technical terms

Small GTPase: A family of proteins that cycle between inactive GDP-bound and active GTP-bound states to relay signals.

CAAX box: A C-terminal motif (Cys–A–A–X) directing prenylation and subsequent proteolytic and methylation steps.

Prenylation: Attachment of lipid groups (farnesyl or geranylgeranyl) to cysteine residues for membrane targeting.

Palmitoylation: Reversible addition of palmitic acid to cysteine residues that stabilises membrane association.

Guanine nucleotide exchange factor (GEF): Protein that activates GTPases by promoting exchange of GDP for GTP.

References

1. C-terminus Proteolysis and Palmitoylation Cooperate for Optimal Plasma Membrane Localization of RasA in Aspergillus fumigatus. Frontiers in Microbiology (2018).
2. SH3‐class Ras guanine nucleotide exchange factors are essential for Aspergillus fumigatus invasive growth. Cellular Microbiology (2019).
3. Ras signalling in pathogenic yeasts. Microbial Cell (2018).
4. A Fungus-Specific Protein Domain Is Essential for RasA-Mediated Morphogenetic Signaling in Aspergillus fumigatus. mSphere (2016).