title: Optogenetic control of nuclear protein export.
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.
authors: Department of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.|Department of Bioinformatics and Functional Genomics, Synthetic Biology Group, Institute for Pharmacy and Biotechnology (IPMB), University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.|Center for Quantitative Analysis of Molecular and Cellular Biosystems (BioQuant), University of Heidelberg, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany.
authors: Dominik
authors: D
authors: Niopek
authors: Department of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors: Pierre
authors: P
authors: Wehler
authors: Department of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors: Julia
authors: J
authors: Roensch
authors: Department of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.|Department of Bioinformatics and Functional Genomics, Synthetic Biology Group, Institute for Pharmacy and Biotechnology (IPMB), University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.|Center for Quantitative Analysis of Molecular and Cellular Biosystems (BioQuant), University of Heidelberg, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany.
authors: Roland
authors: R
authors: Eils
authors: Department of Bioinformatics and Functional Genomics, Synthetic Biology Group, Institute for Pharmacy and Biotechnology (IPMB), University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.|Center for Quantitative Analysis of Molecular and Cellular Biosystems (BioQuant), University of Heidelberg, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany.
authors: Barbara
authors: B
authors: Di Ventura
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007091:Image Processing, Computer-Assisted; D028884:Karyopherins / Q000235:genetics*; D008027:Light; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D062308:Optogenetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D000097606:Exportin 1 Protein
chemical_list: D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D016159:Tumor Suppressor Protein p53; D000097606:Exportin 1 Protein