Figure 1.

Impact of fused in sarcoma (FUS) mislocalization and aggregation. Normal FUS is predominantly localized to the nucleus. Due to defective methylation of the protein or mutations in the nuclear localization signal (NLS), FUS will mislocalize to the cytoplasm, forming aggregates. Cytoplasmic FUS aggregation could result in various unfavorable outcomes, e.g., cytotoxicity and altered mRNA interactions of FUS. Studies show that a relocation of FUS back into the nucleus is possible by e.g., restoring the NLS or various post-translational modifications, thereby reducing the amount of aggregated FUS and cytotoxicity. Further, studies have uncovered new potential suppressors of FUS cytotoxicity, as well as engineered disaggregases that solubilize aggregated FUS.