Spatiotemporal control of interferon-induced JAK/STAT signalling and gene transcription by the retromer complex
Daniela Chmiest,
Nanaocha Sharma,
Natacha Zanin,
Christine Viaris de Lesegno,
Massiullah Shafaq-Zadah,
Vonick Sibut,
Florent Dingli,
Philippe Hupé,
Stephan Wilmes,
Jacob Piehler,
Damarys Loew,
Ludger Johannes,
Gideon Schreiber and
Christophe Lamaze ()
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Daniela Chmiest: Membrane Dynamics and Mechanics of Intracellular Signaling Laboratory, Institut Curie–Centre de Recherche, PSL Research University
Nanaocha Sharma: Weizmann Institute of Science
Natacha Zanin: Membrane Dynamics and Mechanics of Intracellular Signaling Laboratory, Institut Curie–Centre de Recherche, PSL Research University
Christine Viaris de Lesegno: Membrane Dynamics and Mechanics of Intracellular Signaling Laboratory, Institut Curie–Centre de Recherche, PSL Research University
Massiullah Shafaq-Zadah: Institut National de la Santé et de la Recherche Médicale (INSERM) U1143
Vonick Sibut: Bioinformatics and Computational Systems Biology of Cancer, Institut Curie–Centre de Recherche, PSL Research University
Florent Dingli: Proteomics and Mass Spectrometry Laboratory, Institut Curie–Centre de Recherche, PSL Research University
Philippe Hupé: Bioinformatics and Computational Systems Biology of Cancer, Institut Curie–Centre de Recherche, PSL Research University
Stephan Wilmes: University of Osnabrück
Jacob Piehler: University of Osnabrück
Damarys Loew: Proteomics and Mass Spectrometry Laboratory, Institut Curie–Centre de Recherche, PSL Research University
Ludger Johannes: Institut National de la Santé et de la Recherche Médicale (INSERM) U1143
Gideon Schreiber: Weizmann Institute of Science
Christophe Lamaze: Membrane Dynamics and Mechanics of Intracellular Signaling Laboratory, Institut Curie–Centre de Recherche, PSL Research University
Nature Communications, 2016, vol. 7, issue 1, 1-15
Abstract:
Abstract Type-I interferons (IFNs) play a key role in the immune defences against viral and bacterial infections, and in cancer immunosurveillance. We have established that clathrin-dependent endocytosis of the type-I interferon (IFN-α/β) receptor (IFNAR) is required for JAK/STAT signalling. Here we show that the internalized IFNAR1 and IFNAR2 subunits of the IFNAR complex are differentially sorted by the retromer at the early endosome. Binding of the retromer VPS35 subunit to IFNAR2 results in IFNAR2 recycling to the plasma membrane, whereas IFNAR1 is sorted to the lysosome for degradation. Depletion of VPS35 leads to abnormally prolonged residency and association of the IFNAR subunits at the early endosome, resulting in increased activation of STAT1- and IFN-dependent gene transcription. These experimental data establish the retromer complex as a key spatiotemporal regulator of IFNAR endosomal sorting and a new factor in type-I IFN-induced JAK/STAT signalling and gene transcription.
Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13476
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DOI: 10.1038/ncomms13476
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