Molecular Scale

Lipid membrane remodeling by protein, from endocytosis to membrane traffic

Clathrin and Dynamin

Clathrin, by forming spherical cages to deform the membrane, and dynamin by constriction the neck of clathrin-coated buds to fission the membrane, are essential actors of endocytosis. Our lab pioneered of in vitro assays that reconstitute membrane traffic processes. We reconstituted membrane tube pulling by cytoskeleton (Roux et al. PNAS 2002), membrane fission by dynamin (Roux et al. Nature 2006, Morlot et al. Cell 2012). 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) and of BAR proteins binding (Sorre et al. PNAS 2012). We also showed that cell membrane tension is a major regulator of membrane traffic. Dynamin-mediated membrane fission is critically controlled by membrane tension (Roux et al. Nature 2006, Morlot et al. Cell 2012), and clathrin polymerization is controlled by membrane tension (Saleem et al. Nat Comms 2015).


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).