Laboratoire Matière et Systèmes Complexes

Membrane remodelling by protein crowding during formation of intraluminal vesicles

Abstract:

In this talk I will show some of our recent work on how protein crowding can induce membrane remodelling. The major part of the talk will be about the formation of intraluminal vesicles (ILVs), which plays a crucial role in the attenuation of growth factor receptor signalling. The endosomal sorting complex required for transport (ESCRT) machinery mediates this process. The general dogma has been that upstream ESCRTs (0 to II) sequester receptors at the surface of endosomes and the downstream ESCRTs (III/VPS4) remodel the endosome membrane leading to the abscission and formation of receptor-containing ILVs. We now show that upstream ESCRTs not only sequester cargo, but in addition play a crucial role for the initiation of membrane shape remodeling in ILV budding. Through a combination of mathematical modeling and experimental measurements we show that upstream ESCRTs facilitate ILV budding by crowding with a high density in the membrane neck region. Lastly, I will show how we can formulate a generic model for protein crowding that effectively induces a spontaneous curvature that depends on the protein density. The model allows us to predict the membrane shape transformation from a flat patch to spherical buds and elongated pearl-like and tubular shapes as a function of the size of the crowded domain, following experimental observations.

Tuesday March 2nd at 11h (Zoom)