The misplacement of proteins within a cell can cause various diseases, but no therapeutic intervention can precisely control protein location. Writing in Nature, Ng et al. describe targeted relocalization-activating molecules (TRAMs) that couple misplaced proteins to cellular shuttles, relocating them to their proper places.
Ng et al. began by testing a TRAM previously used to bring together two proteins, EcDHFR and FKBP12F36V. They converted EcDHFR into a shuttle protein by adding a nuclear export signal and coupled FKBP12F36V to a target protein in the nucleus, enabling its movement to the cytoplasm upon TRAM treatment.