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Cited by 17Protein Structure and DynamicsMicrotubule and mitosis dynamicsRNA Research and Splicing

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

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Billault-Chaumartin, Ingrid, Muriel, Olivia, Michon, Laetitia, Martin, Sophie G.·2022·Current Biology
DOI 10.1016/j.cub.2022.09.026PMC PMC9671092

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Abstract

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, 1 hyphal steering in filamentous fungi, 2 , 3 and local cell wall digestion preceding the fusion of yeast gametes. 4 During fission yeast Schizosaccharomyces pombe gamete fusion, the actin fusion focus assembled by the formin Fus1 concentrates secretory vesicles carrying cell wall digestive enzymes. 5 , 6 , 7 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, 6 , 8 , 9 , 10 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.

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Metadata

Authors
Billault-Chaumartin, I., Muriel, O., Michon, L., & Martin, S. G.
Affiliations
University of Lausanne (CH)
Corresponding author
Martin, Sophie G.
ORCID
Venue
Current Biology
Publisher
Elsevier BV
Published
2022-11
Volume
32
Issue
21
Pages
4752-4761.e10
ISSN
0960-9822 (ISSN-L)
DOI
10.1016/j.cub.2022.09.026
PMC
PMC9671092
OpenAlex
W4302007698
Cited by
17
References
1
Citations by year
2026: 3 · 2025: 3 · 2024: 7 · 2023: 2 · 2022: 2
FWCI
1.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • SERVAL (Université de Lausanne) (publishedVersion, cc-by)
  • IRIS (submittedVersion, cc-by)
  • HAL (submittedVersion, other-oa)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
Funders
  • National Science Foundation
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (176396, 191990, 310030)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
FUS1, intrinsically disordered regions, cell fusion, cell wall digestion, myosin V, Schizosaccharomyces pombe, protein condensation, low complexity regions, selective permeability, cell lysis
MeSH terms
Formins, Actins, Cell Fusion, Actin Cytoskeleton, Schizosaccharomyces, Schizosaccharomyces pombe Proteins

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