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Phenotypes on demand via switchable target protein degradation in multicellular organisms

Author

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  • Frederik Faden

    (Independent Junior Research Group on Protein Recognition and Degradation, Leibniz Institute of Plant Biochemistry (IPB)
    ScienceCampus Halle—Plant-based Bioeconomy)

  • Thomas Ramezani

    (University Group at the Max Planck Institute for Plant Breeding Research (MPIPZ), Max Delbrück Laboratory
    University of Cologne, Institute of Botany III, Biocenter
    Present address: The Queen’s Medical Research Institute, MRC Centre for Inflammation Research, The University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.)

  • Stefan Mielke

    (Independent Junior Research Group on Protein Recognition and Degradation, Leibniz Institute of Plant Biochemistry (IPB)
    ScienceCampus Halle—Plant-based Bioeconomy)

  • Isabel Almudi

    (Institute of Molecular Systems Biology (IMSB), Swiss Federal Institute of Technology (ETH)
    Present address: Andalusian Centre for Developmental Biology (CABD), Universidad Pablo de Olavide, Ctra. Utrera Km. 1, 41013 Seville, Spain.)

  • Knud Nairz

    (Institute of Molecular Systems Biology (IMSB), Swiss Federal Institute of Technology (ETH)
    Present address: Novino Slowdrink GmbH, Blümlisalpstrasse 31, CH-8006 Zürich, Switzerland and Inselspital Bern, Freiburgstrasse 10, CH-3010 Bern, Switzerland.)

  • Marceli S. Froehlich

    (Institute for Genetics, Biocenter, University of Cologne
    Present address: Grünenthal Innovation—Early Clinical Development, Grünenthal GmbH, Zieglerstraße 6, D-52078 Aachen, Germany.)

  • Jörg Höckendorff

    (Institute for Genetics, Biocenter, University of Cologne
    Present address: UCB BIOSCIENCES GmbH, Alfred-Nobel-Straße 10, D-40789 Monheim, Germany.)

  • Wolfgang Brandt

    (Computational Chemistry, Leibniz Institute of Plant Biochemistry (IPB))

  • Wolfgang Hoehenwarter

    (Proteomics Unit, Leibniz Institute of Plant Biochemistry (IPB))

  • R. Jürgen Dohmen

    (Institute for Genetics, Biocenter, University of Cologne)

  • Arp Schnittger

    (University Group at the Max Planck Institute for Plant Breeding Research (MPIPZ), Max Delbrück Laboratory
    University of Cologne, Institute of Botany III, Biocenter
    Institut de Biologie Moléculaire des Plantes du CNRS, IBMP-CNRS, Unité Propre de Recherche 2357, Conventionné avec l’Université de Strasbourg
    Present address: Department of Developmental Biology, Biozentrum Klein Flottbek, University of Hamburg, Ohnhorststrasse 18, D-22609 Hamburg, Germany.)

  • Nico Dissmeyer

    (Independent Junior Research Group on Protein Recognition and Degradation, Leibniz Institute of Plant Biochemistry (IPB)
    ScienceCampus Halle—Plant-based Bioeconomy
    University Group at the Max Planck Institute for Plant Breeding Research (MPIPZ), Max Delbrück Laboratory
    University of Cologne, Institute of Botany III, Biocenter)

Abstract

Phenotypes on-demand generated by controlling activation and accumulation of proteins of interest are invaluable tools to analyse and engineer biological processes. While temperature-sensitive alleles are frequently used as conditional mutants in microorganisms, they are usually difficult to identify in multicellular species. Here we present a versatile and transferable, genetically stable system based on a low-temperature-controlled N-terminal degradation signal (lt-degron) that allows reversible and switch-like tuning of protein levels under physiological conditions in vivo. Thereby, developmental effects can be triggered and phenotypes on demand generated. The lt-degron was established to produce conditional and cell-type-specific phenotypes and is generally applicable in a wide range of organisms, from eukaryotic microorganisms to plants and poikilothermic animals. We have successfully applied this system to control the abundance and function of transcription factors and different enzymes by tunable protein accumulation.

Suggested Citation

  • Frederik Faden & Thomas Ramezani & Stefan Mielke & Isabel Almudi & Knud Nairz & Marceli S. Froehlich & Jörg Höckendorff & Wolfgang Brandt & Wolfgang Hoehenwarter & R. Jürgen Dohmen & Arp Schnittger & , 2016. "Phenotypes on demand via switchable target protein degradation in multicellular organisms," Nature Communications, Nature, vol. 7(1), pages 1-15, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12202
    DOI: 10.1038/ncomms12202
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