Optogenetic control of nuclear protein export

Nat Commun. 2016 Feb 8:7:10624. doi: 10.1038/ncomms10624.

Abstract

Active nucleocytoplasmic transport is a key mechanism underlying protein regulation in eukaryotes. While nuclear protein import can be controlled in space and time with a portfolio of optogenetic tools, protein export has not been tackled so far. Here we present a light-inducible nuclear export system (LEXY) based on a single, genetically encoded tag, which enables precise spatiotemporal control over the export of tagged proteins. A constitutively nuclear, chromatin-anchored LEXY variant expands the method towards light inhibition of endogenous protein export by sequestering cellular CRM1 receptors. We showcase the utility of LEXY for cell biology applications by regulating a synthetic repressor as well as human p53 transcriptional activity with light. LEXY is a powerful addition to the optogenetic toolbox, allowing various novel applications in synthetic and cell biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / genetics*
  • Animals
  • Cell Line, Tumor
  • Cell Nucleus / metabolism*
  • Cytoplasm / metabolism*
  • Exportin 1 Protein
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Image Processing, Computer-Assisted
  • Karyopherins / genetics*
  • Light*
  • Mice
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Optogenetics
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Karyopherins
  • Receptors, Cytoplasmic and Nuclear
  • Tumor Suppressor Protein p53