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Reference - PMID:36202103 - Condensation of the fusion focus by the intrinsically disordered region of the formin Fus1 is essential for cell-cell fusion.

Reference summary

PubMed ID
PMID:36202103
Title
Condensation of the fusion focus by the intrinsically disordered region of the formin Fus1 is essential for cell-cell fusion.
Authors
Billault-Chaumartin I, Muriel O, Michon L, Martin SG
Citation
Curr Biol 2022 Nov 07;32(21):4752-4761.e10
Publication year
2022
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.

Annotation

Multi-locus phenotype

FYPO:0006386 - protein abnormally dispersed at shmoo tip

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Single locus phenotype

FYPO:0006098 - abnormal protein localization to cytoplasm

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FYPO:0005503 - abnormally monopolar protein localization to cell tip

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FYPO:0000413 - abolished cell fusion during mating

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FYPO:0006505 - abolished protein localization to shmoo tip

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FYPO:0008002 - cell lysis during mating

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FYPO:0007096 - decreased protein localization to actin fusion focus

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FYPO:0008400 - exocytic vesicles present in decreased numbers at the fusion focus of mating cells

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FYPO:0007094 - increased duration of cell fusion during mating

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FYPO:0003532 - increased monopolar index

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FYPO:0007095 - increased protein localization to actin fusion focus

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FYPO:0003482 - increased punctate cytoplasmic protein localization

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FYPO:0008393 - normal cell fusion during mating

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FYPO:0006386 - protein abnormally dispersed at shmoo tip

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FYPO:0003527 - protein mislocalized to cell tip

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