Molecular Scale


ESCRT-III, discovered in the 2000s, became a major focus of research in the field of cell membrane biology because it was found to catalyze all membrane fission reactions in which cytosolic proteins are coming within the membrane neck. It is thus the only membrane remodelling machinery that works on every organelle, and it is probably the earliest one in evolution, as it is the only one present in Archaea, where it is associated with the formation of the endomembrane system. To explain how ESCRT-III can deform membranes, we proposed a buckling spring mechanism for the membrane remodeling function of ESCRT-III (Chiaruttini et al. Cell 2015), and we showed how this deformation process is driven by a Vps4 ATPase sequence (Mierzwa et al. Nat Cell Biol 2017). By reconstituting the full sequence of turnover in vitro, deformation and fission, we were able to understand the mechanism of ESCRT-III membrane remodelling (Pfitzner et al, Cell 2020), combining important information from Cryo-TEM structures obtained in the lab (Moser von Filseck et al. Nat Comms 2020). He showed that membrane tension regulates ESCRT-III-mediated Intra-Lumenal Vesicle formation (Mercier et al. Nat Cell Biol, 2020).

Lipid membrane remodeling by protein, from endocytosis to membrane traffic

Clathrin and Dynamin

Clathrin is a versatile protein that is an essential actor in many cellular processes, such as endocytosis, trans-Golgi network trafficking and endosomal protein sorting. The triskelion-shaped protein assembles in a variety of structures from flat lattices to spherical cages that have the ability to stabilize and deform membranes. Our lab pioneered in vitro assays that reconstitute membrane traffic processes, such as reconstituted membrane tube pulling by cytoskeleton (Roux et al. PNAS 2002). Doing this, we showed that membrane curvature is a critical parameter that controls membrane traffic. Curvature promotes lipid sorting (Roux et al. EMBOj 2005), and critically controls dynamin polymerization (Roux et al. PNAS 2010) as well as BAR proteins binding (Sorre et al. PNAS 2012). We also showed that cell membrane tension is a major regulator of membrane traffic and clathrin polymerization (Saleem et al. Nat Comms 2015). We now focus on understanding how the dynamics of clathrin and its interactions with its many partners modulate the various processes it is involved in. Using in-vitro reconstitution assays as well as live yeast cell TIRF (Total Internal Reflexion Fluorescence) microscopy, we study how clathrin coat assembles on membranes. We also aim to decipher the parameters that govern its role in membrane shape and membrane deformation.