Rapid and reversible dissolution of biomolecular condensates using light-controlled recruitment of a solubility tag
Ellen H. Brumbaugh-Reed, Yang Gao, Kazuhiro Aoki, Jared E. Toettcher
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. Brumbaugh-Reed and colleagues present OptoMBP, an optogenetic strategy for inducing the dissolution of biomolecular condensates. They show that the OptoMBP system can dissolve multiple protein condensates with high spatiotemporal precision.