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Membrane remodeling is a critical process for many membrane trafficking events, including clathrin-mediated endocytosis. Several molecular mechanisms for protein-induced membrane curvature have been described in some detail. Contrary, the effect that the physico-chemical properties of the membrane have on these processes is far less well understood. Here, we show that the membrane binding and curvature-inducing ENTH domain of epsin1 is regulated by phosphatidylserine (PS). ENTH binds to membranes in a PI(4,5)P2-dependent manner but only induces curvature in the presence of PS. On PS-containing membranes, the ENTH domain forms rigid homo-oligomers and assembles into clusters. Membrane binding and membrane remodeling can be separated by structure-to-function mutants. Such oligomerization mutants bind to membranes but do not show membrane remodeling activity. In vivo, they are not able to rescue defects in epidermal growth factor receptor (EGFR) endocytosis in epsin knock-down cells. Together, these data show that the membrane lipid composition is important for the regulation of protein-dependent membrane deformation during clathrin-mediated endocytosis.

Original publication




Journal article


Cell Mol Life Sci

Publication Date





2355 - 2370


Clathrin-mediated endocytosis, ENTH domain, Membrane curvature, Membrane dynamics, Reconstitution of membrane dynamics, Adaptor Proteins, Vesicular Transport, Binding Sites, Cell Membrane, Clathrin, Endocytosis, Humans, Membrane Lipids, Membrane Proteins, Microscopy, Electron, Mutation, Phosphatidylinositol 4,5-Diphosphate, Protein Binding, Protein Domains, Protein Transport