Perturbation of nuclear proteins by optogenetic trapping in Drosophila ovary.

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, nuclear localization sequence (NLS)-light-activated reversible inhibition by assembled trap (LARIAT), by fusing a NLS to LARIAT, enabling light-inducible clustering of diverse GFP-tagged nuclear proteins in Drosophila ovarian cells. NLS-LARIAT-mediated clustering of GFP-tagged transcriptional and epigenetic regulators, such as slow border cells (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 GFP-tagged nuclear structures, including the nuclear envelope and chromatin. Thus, NLS-LARIAT provides a versatile and broadly applicable optogenetic platform for spatiotemporal control of GFP-tagged nuclear proteins, offering new opportunities to dissect nuclear organization and function across model systems.