Active nucleocytoplasmic transport controls the localization and spatiotemporal dynamics of proteins in eukaryotes, thereby governing essential cellular processes including gene expression, cell division and apoptosis. Regulation of protein import and export is achieved mainly by masking and unmasking of nuclear import and nuclear export signals (NLSs and NESs) directly located within the polypeptide or by binding and unbinding to NLS- and NES-bearing partners.
Optogenetic tools that enable controlling with light the nuclear import of tagged proteins in mammalian cells and yeast have been reported, but no optogenetic tools are yet available to directly control protein export. However, such a tool would have enormous application potential, for example, for regulating the activity of nuclear or cytoplasmic signalling molecules, and would complement the existing optogenetic toolset for control of nuclear import protein dimerization and oligomerization, membrane recruitment and organelle transport and positioning.
Researchers present LEXY, a blue light-induced nuclear export system based on a single, genetically encoded tag, enabling dynamic and spatial control over nuclear protein export. They show fast and fully reversible nuclear export of LEXYtagged proteins of diverse nature and origin in various cell lines.
A chromatin-anchored LEXY variant mediates light-inducible sequestration of cellular CRM1, the primary nuclear export receptor, thereby allowing inhibition of endogenous nuclear export. To demonstrate the utility of LEXY for applications in synthetic and cell biology, they regulate synthetic repressors as well as the transcriptional activity of human p53 with light.
Therefore LEXY could a powerful addition to the optogenetic toolbox, allowing various novel applications in synthetic and cell biology.