Cooperativity of membrane-protein and protein-protein interactions control membrane remodeling by epsin 1 and affects clathrin-mediated endocytosis.

Cooperativity of membrane-protein and protein-protein interactions control membrane remodeling by epsin 1 and affects clathrin-mediated endocytosis.
Cell Mol Life Sci. 2020 Sep 30;:
Authors: Kroppen B, Teske N, Yambire KF, Denkert N, Mukherjee I, Tarasenko D, Jaipuria G, Zweckstetter M, Milosevic I, Steinem C, Meinecke M
Abstract
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 defor...

Source: Cellular and Molecular Life Sciences : CMLS - September 29, 2020 Category: Cytology Authors: Kroppen B, Teske N, Yambire KF, Denkert N, Mukherjee I, Tarasenko D, Jaipuria G, Zweckstetter M, Milosevic I, Steinem C, Meinecke M Tags: Cell Mol Life Sci Source Type: research