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Rapid and reversible dissolution of biomolecular condensates using light-controlled recruitment of a solubility tag

Author

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  • Ellen H. Brumbaugh-Reed

    (Princeton University
    Princeton University
    National Institutes of Natural Sciences)

  • Yang Gao

    (Princeton University)

  • Kazuhiro Aoki

    (National Institutes of Natural Sciences
    Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences
    National Institute for Basic Biology, National Institutes of Natural Sciences
    SOKENDAI (The Graduate University for Advanced Studies))

  • Jared E. Toettcher

    (Princeton University
    Princeton University)

Abstract

Biomolecular condensates are broadly implicated in both normal cellular regulation and disease. Consequently, several chemical biology and optogenetic approaches have been developed to induce phase separation of a protein of interest. However, few tools are available to perform the converse function – dissolving a condensate of interest on demand. Such a tool would aid in testing whether the condensate plays specific functional roles. Here we show that light-gated recruitment of a solubilizing domain, maltose-binding protein (MBP), results in rapid and controlled dissolution of condensates formed from proteins of interest. Our optogenetic MBP-based dissolution strategy (OptoMBP) is rapid, reversible, and can be spatially controlled with subcellular precision. We also provide a proof-of-principle application of OptoMBP by disrupting condensation of the oncogenic fusion protein FUS-CHOP and reverting FUS-CHOP driven transcriptional changes. We envision that the OptoMBP system could be broadly useful for disrupting constitutive protein condensates to probe their biological functions.

Suggested Citation

  • Ellen H. Brumbaugh-Reed & Yang Gao & Kazuhiro Aoki & Jared E. Toettcher, 2024. "Rapid and reversible dissolution of biomolecular condensates using light-controlled recruitment of a solubility tag," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50858-0
    DOI: 10.1038/s41467-024-50858-0
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    References listed on IDEAS

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