title: The endosomal transcriptional regulator RNF11 integrates degradation and transport of EGFR.
abstract: Stimulation of cells with epidermal growth factor (EGF) induces internalization and partial degradation of the EGF receptor (EGFR) by the endo-lysosomal pathway. For continuous cell functioning, EGFR plasma membrane levels are maintained by transporting newly synthesized EGFRs to the cell surface. The regulation of this process is largely unknown. In this study, we find that EGF stimulation specifically increases the transport efficiency of newly synthesized EGFRs from the endoplasmic reticulum to the plasma membrane. This coincides with an up-regulation of the inner coat protein complex II (COPII) components SEC23B, SEC24B, and SEC24D, which we show to be specifically required for EGFR transport. Up-regulation of these COPII components requires the transcriptional regulator RNF11, which localizes to early endosomes and appears additionally in the cell nucleus upon continuous EGF stimulation. Collectively, our work identifies a new regulatory mechanism that integrates the degradation and transport of EGFR in order to maintain its physiological levels at the plasma membrane.
authors.affiliation: Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
authors.forename: Sandra
authors.identifier: http://orcid.org/0000-0001-9428-3213
authors.initials: S
authors.lastname: Scharaw
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
authors.forename: Murat
authors.identifier: http://orcid.org/0000-0001-8603-4313
authors.initials: M
authors.lastname: Iskar
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
authors.forename: Alessandro
authors.identifier: http://orcid.org/0000-0002-3046-0871
authors.initials: A
authors.lastname: Ori
authors.affiliation: Institut Curie, Paris Sciences et Lettres Research University, 75248 Paris, France.|Institut Curie, Centre National de la Recherche Scientifique UMR144, 75248 Paris, France.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Boncompain
authors.affiliation: Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
authors.forename: Vibor
authors.initials: V
authors.lastname: Laketa
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Poser
authors.affiliation: Science for Life Laboratory, KTH Royal Institute of Technology, 17121 Solna, Sweden.
authors.forename: Emma
authors.identifier: http://orcid.org/0000-0001-7034-0850
authors.initials: E
authors.lastname: Lundberg
authors.affiliation: Institut Curie, Paris Sciences et Lettres Research University, 75248 Paris, France.|Institut Curie, Centre National de la Recherche Scientifique UMR144, 75248 Paris, France.
authors.forename: Franck
authors.identifier: http://orcid.org/0000-0002-9129-9401
authors.initials: F
authors.lastname: Perez
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Beck
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.|Max Delbrueck Center for Molecular Medicine, 13125 Berlin, Germany.|Department of Bioinformatics, Biocenter, University of Wuerzburg, 97074 Wuerzburg, Germany.
authors.forename: Peer
authors.initials: P
authors.lastname: Bork
authors.affiliation: Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany pepperko@embl.de.
authors.forename: Rainer
authors.identifier: http://orcid.org/0000-0002-9762-3583
authors.initials: R
authors.lastname: Pepperkok
mesh_terms: D022181:COP-Coated Vesicles / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D049452:Green Fluorescent Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C404508:RNF11 protein, human; C485184:enhanced green fluorescent protein