Stat-mediated Signaling Induced by Type I and Type II Interferons (IFNs) Is Differentially Controlled through Lipid Microdomain Association and Clathrin-dependent Endocytosis of IFN Receptors
| Autor: | Ludger Johannes, Pierre Eid, Keith Mitchell, Christophe Lamaze, Marie-Noëlle Monier, Florence Baychelier, Alexandre Fradagrada, Marta Marchetti |
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| Přispěvatelé: | Unité mixte de recherche interactions plantes-microorganismes, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut Curie [Paris], Oncologie virale (OV), Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2006 |
| Předmět: |
Transcription
Genetic [SDV]Life Sciences [q-bio] Active Transport Cell Nucleus Receptor Interferon alpha-beta Response Elements stat Interferon-gamma 03 medical and health sciences Membrane Microdomains 0302 clinical medicine Humans [SDV.BV]Life Sciences [q-bio]/Vegetal Biology STAT1 Receptor Molecular Biology Receptors Interferon 030304 developmental biology 0303 health sciences biology Cell Membrane Lipid microdomain Interferon-alpha Membrane Proteins STAT2 Transcription Factor Articles Cell Biology Receptor-mediated endocytosis Clathrin Endocytosis Cell biology Protein Transport STAT1 Transcription Factor [SDE]Environmental Sciences STAT protein biology.protein 030217 neurology & neurosurgery |
| Zdroj: | Molecular Biology of the Cell Molecular Biology of the Cell, American Society for Cell Biology, 2006, 17 (7), pp.2896-909. ⟨10.1091/mbc.e06-01-0076⟩ |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e06-01-0076 |
| Popis: | International audience; Type I (alpha/beta) and type II (gamma) interferons (IFNs) bind to distinct receptors, although they activate the same signal transducer and activator of transcription, Stat1, raising the question of how signal specificity is maintained. Here, we have characterized the sorting of IFN receptors (IFN-Rs) at the plasma membrane and the role it plays in IFN-dependent signaling and biological activities. We show that both IFN-alpha and IFN-gamma receptors are internalized by a classical clathrin- and dynamin-dependent endocytic pathway. Although inhibition of clathrin-dependent endocytosis blocked the uptake of IFN-alpha and IFN-gamma receptors, this inhibition only affected IFN-alpha-induced Stat1 and Stat2 signaling. Furthermore, the antiviral and antiproliferative activities induced by IFN-alpha but not IFN-gamma were also affected. Finally, we show that, unlike IFN-alpha receptors, activated IFN-gamma receptors rapidly become enriched in plasma membrane lipid microdomains. We conclude that IFN-R compartmentalization at the plasma membrane, through clathrin-dependent endocytosis and lipid-based microdomains, plays a critical role in the signaling and biological responses induced by IFNs and contributes to establishing specificity within the Jak/Stat signaling pathway. |
| Databáze: | OpenAIRE |
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