Membrane Dynamics and Mechanics of Intracellular Signaling

Lamaze

Christophe Lamaze Team leader, DR1 INSERM Tel:

Projects developed in the “Membrane Dynamics and Mechanics of Intracellular Signaling” team are based on the new concepts and original assays developed by the team for the last ten years to investigate the Cell Biology of membrane trafficking and mechanics and its role in intracellular signaling.

The team focuses its effort on three mains directions:

1 – Molecular control of JAK/STAT signaling by endosomal sorting of interferon receptors (IFN-Rs). Following our pioneering studies on EGF signaling, we wish now to identify the molecular machinery that couples IFN-R endocytosis and endosomal sorting with JAK/STAT signaling.

Distinct membrane sorting and trafficking of the IFN- and IFN- receptors play a key role in selective JAK/STAT activation.
Fig.1 | Distinct membrane sorting and trafficking of the IFN-a and IFN-y receptors play a key role in selective JAK/STAT activation.

2 – Understanding the new mechanical role of caveolae in signaling and pathophysiology. We have recently revealed a new role for caveolae, a subset of membrane invaginations present at the cell surface and have established that their disassembly /reassembly cycle represents the primary cell response to mechanical stress (Cell, 2011; Fig. 1). We wish now to understand and identify the molecular players and signaling pathways involved in the caveolae-dependent mechanical response in cancer cell proliferation, muscle dystrophies and atherosclerosis.

Fig.2 | Les cellules répondent à des contraintes mécaniques aigues par le désassemblage et le réassemblage rapide de cavéoles. Au repos, les cavéoles de la membrane plasmique sont principalement sous forme invaginée. Lors de sollicitations mécaniques aigues (choc hypo-osmotique ou étirement), les cavéoles s'aplatissent dans la membrane plasmique et apportent ainsi un excès de membrane ce qui permet de tamponner les variations de tension de membrane. Cela conduit également à une perte des interactions moléculaires de la cavéoline (Cav1) avec ses partenaires (Cavin-1). Nous émettons l'hypothèse que la libération mécanique des principaux constituants des cavéoles est une étape clé de la mécanotransduction. Le retour à des conditions de repos permet le réassemblage de la structure cavéolaire (Sinha et al, 2011 cellules;. Nassoy et Lamaze, Trends Cell Biol 2012).
Fig.2 | Cells respond to acute mechanical stresses by rapid disassembly and reassembly of caveolae. In resting conditions, caveolae at the plasma membrane are mostly budded. Upon acute mechanical stress (hypo-osmotic shock or stretching), caveolae flatten out in the plasma membrane to provide additional membrane and buffer membrane tension. This leads also to a loss of Cav1 and Cavin-1 interaction. We hypothesize that the mechanical release of caveolae main constituents is key step in mechanosignaling. Return to resting conditions allows the reassembly of the caveolar structure (Sinha et al., 2011 Cell; Nassoy and Lamaze, Trends Cell Biol 2012).

3 – Investigating the role of membrane trafficking in cholesterol transcriptional homeostasis. In particular, we are investigating the role of caveolae and shear stress in cholesterol homeostasis in human endothelial cells.

Key publications

Year of 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
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
Cédric M Blouin, Yannick Hamon, Pauline Gonnord, Cédric Boularan, Jérémy Kagan, Christine Viaris de Lesegno, Richard Ruez, Sébastien Mailfert, Nicolas Bertaux, Damarys Loew, Christian Wunder, Ludger Johannes, Guillaume Vogt, Francesc-Xabier Contreras, Didier Marguet, Jean-Laurent Casanova, Céline Galès, Hai-Tao He, Christophe Lamaze (2016 Aug 9)

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

Cell : 920-34 : DOI : 10.1016/j.cell.2016.07.003

Year of publication 2015

Renard, H.F., M. Simunovic, J. Lemiere, E. Boucrot, M.D. Garcia-Castillo, S. Arumugam, V. Chambon, C. Lamaze, C. Wunder, A.K. Kenworthy, A.A. Schmidt, H.T. McMahon, C. Sykes, P. Bassereau, L. Johannes (2015 Jan 22)

Endophilin-A2 functions in membrane scission in clathrin-independent endocytosis

Nature : 517 : 493-496 : DOI : doi:10.1038/nature14064

Year of publication 2013

Emmanuelle Girard, Daniela Chmiest, Natalie Fournier, Ludger Johannes, Jean-Louis Paul, Benoît Vedie, Christophe Lamaze (2013 Sep 17)

Rab7 is functionally required for selective cargo sorting at the early endosome.

Traffic (Copenhagen, Denmark) : 309-26 : DOI : 10.1111/tra.12143

Year of publication 2012

Pierre Nassoy, Christophe Lamaze (2012 Feb 22)

Stressing caveolae new role in cell mechanics.

Trends in cell biology : 381-9 : DOI : 10.1016/j.tcb.2012.04.007
All publications