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Condensation of the fusion focus by the intrinsically disordered region of the formin Fus1 is essential for cell-cell fusion

2022; Elsevier BV; Volume: 32; Issue: 21 Linguagem: Inglês

10.1016/j.cub.2022.09.026

1879-0445

Ingrid Billault-Chaumartin, Olivia Muriel, Laetitia Michon, Sophie G. Martin,

RNA Research and Splicing

Secretory vesicle clusters transported on actin filaments by myosin V motors for local secretion underlie various cellular processes, such as neurotransmitter release at neuronal synapses,1Reshetniak S. Rizzoli S.O. The vesicle cluster as a major organizer of synaptic composition in the short-term and long-term.Curr. Opin. Cell Biol. 2021; 71: 63-68https://doi.org/10.1016/j.ceb.2021.02.007Crossref PubMed Scopus (11) Google Scholar hyphal steering in filamentous fungi,2Riquelme M. Sánchez-León E. The Spitzenkörper: a choreographer of fungal growth and morphogenesis.Curr. Opin. Microbiol. 2014; 20: 27-33https://doi.org/10.1016/j.mib.2014.04.003Crossref PubMed Scopus (77) Google Scholar,3Roberson R.W. Subcellular structure and behaviour in fungal hyphae.J. Microsc. 2020; 280: 75-85https://doi.org/10.1111/jmi.12945Crossref PubMed Scopus (7) Google Scholar and local cell wall digestion preceding the fusion of yeast gametes.4Sieber B. Coronas-Serna J.M. Martin S.G. A focus on yeast mating: from pheromone signaling to cell-cell fusion.Semin. Cell Dev. Biol. 2022; https://doi.org/10.1016/j.semcdb.2022.02.003Crossref Scopus (13) Google Scholar During fission yeast Schizosaccharomyces pombe gamete fusion, the actin fusion focus assembled by the formin Fus1 concentrates secretory vesicles carrying cell wall digestive enzymes.5Petersen J. Weilguny D. Egel R. Nielsen O. Characterization of fus1 of Schizosaccharomyces pombe: a developmentally controlled function needed for conjugation.Mol. Cell. Biol. 1995; 15: 3697-3707https://doi.org/10.1128/MCB.15.7.3697Crossref PubMed Scopus (94) Google Scholar,6Dudin O. Bendezú F.O. Groux R. Laroche T. Seitz A. Martin S.G. A formin-nucleated actin aster concentrates cell wall hydrolases for cell fusion in fission yeast.J. Cell Biol. 2015; 208: 897-911https://doi.org/10.1083/jcb.201411124Crossref PubMed Scopus (44) Google Scholar,7Muriel O. Michon L. Kukulski W. Martin S.G. Ultrastructural plasma membrane asymmetries in tension and curvature promote yeast cell fusion.J. Cell Biol. 2021; 220: e202103142https://doi.org/10.1083/jcb.202103142Crossref PubMed Scopus (9) Google Scholar The position and coalescence of the vesicle focus are controlled by local signaling and actin-binding proteins to prevent inappropriate cell wall digestion that would cause lysis,6Dudin O. Bendezú F.O. Groux R. Laroche T. Seitz A. Martin S.G. A formin-nucleated actin aster concentrates cell wall hydrolases for cell fusion in fission yeast.J. Cell Biol. 2015; 208: 897-911https://doi.org/10.1083/jcb.201411124Crossref PubMed Scopus (44) Google Scholar,8Dudin O. Merlini L. Martin S.G. Spatial focalization of pheromone/MAPK signaling triggers commitment to cell-cell fusion.Genes Dev. 2016; 30: 2226-2239https://doi.org/10.1101/gad.286922.116Crossref PubMed Scopus (25) Google Scholar,9Merlini L. Khalili B. Dudin O. Michon L. Vincenzetti V. Martin S.G. Inhibition of Ras activity coordinates cell fusion with cell-cell contact during yeast mating.J. Cell Biol. 2018; 217: 1467-1483https://doi.org/10.1083/jcb.201708195Crossref PubMed Scopus (16) Google Scholar,10Dudin O. Merlini L. Bendezú F.O. Groux R. Vincenzetti V. Martin S.G. A systematic screen for morphological abnormalities during fission yeast sexual reproduction identifies a mechanism of actin aster formation for cell fusion.PLoS Genet. 2017; 13: e1006721https://doi.org/10.1371/journal.pgen.1006721Crossref PubMed Scopus (23) Google Scholar but the mechanisms of focusing have been elusive. Here, we show that the regulatory N terminus of Fus1 contains an intrinsically disordered region (IDR) that mediates Fus1 condensation in vivo and forms dense assemblies that exclude ribosomes. Fus1 lacking its IDR fails to concentrate in a tight focus and causes cell lysis during attempted cell fusion. Remarkably, the replacement of Fus1 IDR with a heterologous low-complexity region that forms molecular condensates fully restores Fus1 focusing and function. By contrast, the replacement of Fus1 IDR with a domain that forms more stable oligomers restores focusing but poorly supports cell fusion, suggesting that condensation is tuned to yield a selectively permeable structure. We propose that condensation of actin structures by an IDR may be a general mechanism for actin network organization and the selective local concentration of secretory vesicles.