Perturbation of nuclear proteins by optogenetic trapping in Drosophila ovary

Abstract

The eukaryotic nucleus hosts transcription factors and other numerous nuclear proteins essential for genome organization and function. Optogenetic tools have been applied to match nuclear protein dynamics but remain largely confined to transcription factors, leaving most nuclear proteins inaccessible for precise manipulation. Here, we engineered an optogenetic tool, NLS-LARIAT, by fusing a nuclear localization sequence to the LARIAT (light-activated reversible inhibition by assembled trap), enabling light-inducible clustering of diverse GFP-tagged nuclear proteins in Drosophila ovarian cells. NLS-LARIAT-mediated clustering of transcriptional and epigenetic regulators, such as Slbo and LSD1, phenocopied genetic inhibition while revealing rapid and localized roles of Slbo during border cell migration. Beyond regulatory factors, NLS-LARIAT can also be used to manipulate nuclear structures including the nuclear envelope and chromatin. Thus, NLS-LARIAT provides a versatile and broadly applicable optogenetic platform for spatiotemporal control of nuclear proteins, offering new opportunities to dissect nuclear organization and function across model systems.