Zanin, Natacha, de Lesegno, Christine Viaris, Podkalicka, Joanna, Meyer, Thomas, Troncoso, Pamela Gonzalez, Bun, Philippe, Danglot, Lydia, Chmiest, Daniela, Urbe, Sylvie 
ORCID: 0000-0003-4735-9814, Piehler, Jacob et al (show 2 more authors)
(2023)
STAM and Hrs interact sequentially with IFN-α Receptor to control spatiotemporal JAK-STAT endosomal activation.
NATURE CELL BIOLOGY, 25 (3).
425-+.
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Zanin et al Accepted NCB2023.pdf - Author Accepted Manuscript Download (20MB) | Preview |
Abstract
Activation of the JAK-STAT pathway by type I interferons (IFNs) requires clathrin-dependent endocytosis of the IFN-α and -β receptor (IFNAR), indicating a role for endosomal sorting in this process. The molecular machinery that brings the selective activation of IFN-α/β-induced JAK-STAT signalling on endosomes remains unknown. Here we show that the constitutive association of STAM with IFNAR1 and TYK2 kinase at the plasma membrane prevents TYK2 activation by type I IFNs. IFN-α-stimulated IFNAR endocytosis delivers the STAM-IFNAR complex to early endosomes where it interacts with Hrs, thereby relieving TYK2 inhibition by STAM and triggering signalling of IFNAR at the endosome. In contrast, when stimulated by IFN-β, IFNAR signalling occurs independently of Hrs as IFNAR is sorted to a distinct endosomal subdomain. Our results identify the molecular machinery that controls the spatiotemporal activation of IFNAR by IFN-α and establish the central role of endosomal sorting in the differential regulation of JAK-STAT signalling by IFN-α and IFN-β.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Endosomes, Interferon Type I, Interferon-alpha, Signal Transduction, STAT Transcription Factors, Receptor, Interferon alpha-beta, Janus Kinases |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 21 Feb 2023 14:45 |
| Last Modified: | 19 Oct 2023 09:26 |
| DOI: | 10.1038/s41556-022-01085-6 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3168531 |
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