G Protein-Coupled Receptor Signaling in Fungal Systems

G protein-coupled receptor (GPCR) signalling constitutes a fundamental mechanism by which fungi perceive and respond to a wide array of external cues, including nutrients, environmental stresses, pheromones and endogenous lipid mediators. Fungal genomes encode diverse GPCR families that sense sugars, amino acids, oxylipins and quorum-sensing molecules; upon ligand binding, these seven‐transmembrane receptors activate heterotrimeric G-proteins, which in turn regulate effectors such as adenylate cyclase, phospholipase C and mitogen-activated protein kinases. The consequent generation of second messengers—most notably cyclic AMP—activates protein kinase A and other downstream pathways, ultimately modulating gene expression programmes governing spore germination, hyphal growth, sexual and asexual development, stress adaptation and secondary metabolite production. Signal attenuation is mediated by regulators of G-protein signalling, ensuring temporal and spatial control. Advances in structural biology have begun to reveal fungal GPCR architectures, facilitating target-based approaches in antifungal design. Given the roles of GPCRs in the pathogenesis of human and plant pathogens, control of mycotoxin biosynthesis and industrial fermentation processes, a deeper understanding of fungal GPCR networks offers significant opportunities to develop novel therapeutic, agricultural and biotechnological strategies.

Research from Nature Portfolio

Recent studies have unveiled endogenously produced fungal oxylipins as autocrine signals that orchestrate developmental switches in filamentous species. One such oxylipin, 5,8-diHODE, was shown to induce lateral branching and appressorium formation via specific GPCR-mediated pathways in Aspergillus and Magnaporthe species. Transcriptomic profiling following ligand stimulation revealed differential expression of numerous transcription factors, and genetic screens identified regulators that gate branching responses, pinpointing molecular nodes that integrate GPCR activation with morphogenetic programmes. These findings expose an intrinsic signalling system that governs fungal morphogenesis and opens potential avenues for modulating development.

G Protein-Coupled Receptor Signaling in Fungal Systems publication trend

The graph below shows the total number of articles in g protein-coupled receptor signaling in fungal systems across all publications each year (not limited to Nature Index journals).

Technical terms

G Protein-Coupled Receptor (GPCR): A seven‐transmembrane receptor that binds extracellular ligands and activates intracellular G-proteins.

Heterotrimeric G-protein: A complex of Gα, Gβ and Gγ subunits that transduces signals from GPCRs to downstream effectors.

cAMP (cyclic adenosine monophosphate): A second messenger produced by adenylate cyclase that activates protein kinase A and other targets.

Protein kinase A (PKA): A serine/threonine kinase activated by cAMP, which phosphorylates effectors to regulate fungal growth and development.

Quorum sensing: A mechanism of population-density-dependent signalling in which secreted molecules coordinate collective behaviours.

References

1. Developing novel antifungals: lessons from G protein-coupled receptors. Trends in Pharmacological Sciences (2023).
2. Glucose and HODEs regulate Aspergillus ochraceus quorum sensing through the GprC-AcyA pathway. Cellular and Molecular Life Sciences (2024).
3. Deciphering the regulatory mechanisms of the cAMP/protein kinase A pathway and their roles in the pathogenicity of Candida auris. Microbiology Spectrum (2023).
4. Fungal oxylipins direct programmed developmental switches in filamentous fungi. Nature Communications (2020).