Dynamique et mécanique membranaires de la signalisation intracellulaire

Publications de l’équipe

Année de publication : 2016

Blouin CM, Hamon Y, Gonnord P, Boularan C, Kagan J, Viaris de Lesegno C, Ruez R, Mailfert S, Bertaux N, Loew D, Wunder C, Johannes L,Vogt G, Contreras FX, Marguet D, Casanova JL, Galès C, He HT, Lamaze C. (2016 Dec 11)

Glycosylation-Dependent IFN-γR Partitioning in Lipid and Actin Nanodomains Is Critical for JAK Activation

Cell : Volume 166, Issue 4 : 920–934 : DOI : doi.org/10.1016/j.cell.2016.07.003 En savoir plus
Résumé

Understanding how membrane nanoscale organization controls transmembrane receptors signaling activity remains a challenge. We studied interferon-γ receptor (IFN-γR) signaling in fibroblasts from homozygous patients with a T168N mutation in IFNGR2. By adding a neo-N-glycan on IFN-γR2 subunit, this mutation blocks IFN-γ activity by unknown mechanisms. We show that the lateral diffusion of IFN-γR2 is confined by sphingolipid/cholesterol nanodomains. In contrast, the IFN-γR2 T168N mutant diffusion is confined by distinct actin nanodomains where conformational changes required for Janus-activated tyrosine kinase/signal transducer and activator of transcription (JAK/STAT) activation by IFN-γ could not occur. Removing IFN-γR2 T168N-bound galectins restored lateral diffusion in lipid nanodomains and JAK/STAT signaling in patient cells, whereas adding galectins impaired these processes in control cells. These experiments prove the critical role of dynamic receptor interactions with actin and lipid nanodomains and reveal a new function for receptor glycosylation and galectins. Our study establishes the physiological relevance of membrane nanodomains in the control of transmembrane receptor signaling in vivo. VIDEO ABSTRACT.

Replier
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, Christophe Lamaze (2016 Dec 6)

Spatiotemporal control of interferon-induced JAK/STAT signalling and gene transcription by the retromer complex.

Nature communications : 13476 : DOI : 10.1038/ncomms13476 En savoir plus
Résumé

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.

Replier
Christophe Lamaze, Cédric M Blouin (2016 Oct 14)

Receptor Lipid nanodomain Partitioning and Signaling.

Cell cycle (Georgetown, Tex.) : 0 En savoir plus
Résumé

Replier
Camille Kieffer, Ye Wang, Fatma Bagca, Christophe Lamaze (2016 Sep 13)

[Butterfly effect and cancer: how a mechanical pressure induced in vivo leads to tumorigenesis in neighboring healthy cells].

Médecine sciences : M/S : 713-5 : DOI : 10.1051/medsci/20163208017 En savoir plus
Résumé

Replier