Signal transduction by caveolae mechanics
We have established that caveolae are dynamic mechanosensors that buffer cell membrane tension variations to protect the cell against mechanical stress. We have now investigated the role of caveolae mechanics in cell signaling. We found that the mechanical disassembly of caveolae increases the amount of non caveolar caveolin-1 at the plasma membrane and releases the EHD2 ATPase from the neck of caveolae. I will show how these two events are critically involved in the regulation of JAK/STAT signaling and gene transcription. Our data link for the first time caveolae mechanosensing to intracellular signaling and establish caveolae as key mechanosignaling devices.

Christophe Lamaze is a former resident in medical biology who graduated in Pharmacy (Paris V University) and in Cell Biology (Paris XI University). He is Director of Research, 1st Class at INSERM and Deputy Director of the “Cellular & Chemical Biology” Department at the Institut Curie, where he heads the laboratory “Membrane Mechanics and Dynamics of Intracellular Signaling”. Early on, he focused his research on endocytosis and intracellular trafficking. As a post-doctoral fellow with Dr. SL Schmid at the Scripps Research Institute in La Jolla, California (1992-97), he established the key role of endocytosis in intracellular signaling (Science 1996; Nature 1996), a pioneering work opening a new field of investigation, and leading to the concept of the “signaling endosome”. In 1997, he joined the Institut Pasteur where he characterized the first clathrin-independent endocytosis known today as the FEME pathway (Mol. Cell 2001). He set up his own team at the Institut Curie in 2001 to study the role of cell membranes dynamics in signaling, focusing on the interferon receptor and JAK/STAT signaling (Cell, 2016, Nature Commun. 2016). In 2011, his team established that caveolae are mechanosensors that provide protection for cells under mechanical stress (Cell 2011).
Date: 25 March 2019, 12:00 (Monday, 11th week, Hilary 2019)
Venue: Kennedy Institute of Rheumatology, Headington OX3 7FY
Venue Details: Bernard Sunley Theatre
Speaker: Prof Christophe Lamaze (Curie Institute, Paris, France)
Organising department: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS)
Organisers: Laura Sánchez Lazo (Kennedy Institute of Rheumatology), Professor Irina Udalova (Kennedy Institute of Rheumatology), Jo Silva (NDORMS), Wulf Forrester-Barker (University of Oxford, Nuffield Dept of Orthopaedics Rheumatology and Musculoskeletal Sciences)
Host: Prof Claudia Monaco (University of Oxford)
Part of: Kennedy Institute Seminars
Booking required?: Not required
Audience: Members of the University only
Editors: Laura Sanchez Lazo, Abigail Ludlow