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Phase separation in fungi

Abstract

Phase separation, in which macromolecules partition into a concentrated phase that is immiscible with a dilute phase, is involved with fundamental cellular processes across the tree of life. We review the principles of phase separation and highlight how it impacts diverse processes in the fungal kingdom. These include the regulation of autophagy, cell signalling pathways, transcriptional circuits and the establishment of asymmetry in fungal cells. We describe examples of stable, phase-separated assemblies including membraneless organelles such as the nucleolus as well as transient condensates that also arise through phase separation and enable cells to rapidly and reversibly respond to important environmental cues. We showcase how research into phase separation in model yeasts, such as Saccharomyces cerevisiae and Schizosaccharomyces pombe, in conjunction with that in plant and human fungal pathogens, such as Ashbya gossypii and Candida albicans, is continuing to enrich our understanding of fundamental molecular processes.

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Fig. 1: Stress-granule and P-body formation in response to environmental changes.
Fig. 2: Effect of molecular crowding on phase separation.
Fig. 3: Phase separation in polarized growth, cell asymmetry and nuclear divisions.
Fig. 4: Phase separation regulation of bulk and selective autophagy.
Fig. 5: Phase separation regulates transcription and fungal cell fate.

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Acknowledgements

We thank the members of the Bennett laboratory for useful discussions and B. Tu (UTSW) for feedback on sections of the review. Work in the Bennett laboratory is supported by NIAID grant nos AI141893, AI081704 and AI166869, and work in the Fawzi laboratory is supported by NSF BIO 1845734 and NINDS R01NS116176.

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M.I.S. wrote the initial draft, which was extensively revised by R.J.B. and C.F., with input from N.L.F.

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Correspondence to Richard J. Bennett.

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N.L.F. is a member of the scientific advisory board of Dewpoint Therapeutics.

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Staples, M.I., Frazer, C., Fawzi, N.L. et al. Phase separation in fungi. Nat Microbiol 8, 375–386 (2023). https://doi.org/10.1038/s41564-022-01314-6

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