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  • Review Article
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Fungal G-protein-coupled receptors: mediators of pathogenesis and targets for disease control

Abstract

G-protein signalling pathways are involved in sensing the environment, enabling fungi to coordinate cell function, metabolism and development with their surroundings, thereby promoting their survival, propagation and virulence. G-protein-coupled receptors (GPCRs) are the largest class of cell surface receptors in fungi. Despite the apparent importance of GPCR signalling to fungal biology and virulence, relatively few GPCR–G-protein interactions, and even fewer receptor-binding ligands, have been identified. Approximately 40% of current pharmaceuticals target human GPCRs, due to their cell surface location and central role in cell signalling. Fungal GPCRs do not belong to any of the mammalian receptor classes, making them druggable targets for antifungal development. This Review Article evaluates developments in our understanding of fungal GPCR-mediated signalling, while substantiating the rationale for considering these receptors as potential antifungal targets. The need for insights into the structure–function relationship of receptor–ligand interactions is highlighted, which could facilitate the development of receptor-interfering compounds that could be used in disease control.

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Fig. 1: Fungal GPCRs and their downstream signal transduction pathways.
Fig. 2: Classification and distribution of GPCRs in model fungi.
Fig. 3: GPCR-mediated regulation of fungal virulence in mammalian and plant hosts.
Fig. 4: Trans-kingdom communication, GPCR-mediated signalling and disease.

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Acknowledgements

Rothamsted Research receives grant-aided support from the Biotechnology and Biological Sciences Research Council (BBSRC) UK as part of the Institute Strategic Programmes 20:20 wheat [BB/J/00426X/1] and Designing Future Wheat [BB/P016855/1]. N.A.B. was supported by the BBSRC Future Leader Fellowship [BB/N011686/1]. The BBSRC funds open access publication. G.H.G. was supported by Fundação de Amparo a Pesquisa de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), both from Brazil. P.v.D. was supported by grants from the Fund for Scientific Research Flanders (G0D4813N; G062616N), by the KU Leuven Research Fund (GOA/13/006) and by the Interuniversity Attraction Poles Programme initiated by the Belgian Science Policy Office (programme IAP P7/28). S.S. was supported by a grant from the IWT. We would like to thank N. Vangoethem (VIB-KU Leuven) for assisting in the production of the figures.

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N.A.B. and G.H.G. conceptually designed and prepared the manuscript. S.S. and P.v.D. contributed to the preparation of the manuscript.

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Brown, N.A., Schrevens, S., van Dijck, P. et al. Fungal G-protein-coupled receptors: mediators of pathogenesis and targets for disease control. Nat Microbiol 3, 402–414 (2018). https://doi.org/10.1038/s41564-018-0127-5

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