Neutron reflectometry studies of clathrin-mediated endocytosis: effect of modulators FCHO/Eps15
Clathrin-mediated endocytosis (CME) is the main mechanism by which eukaryotic cells internalize and recycle most membrane proteins (termed cargo). CME is a fairly well understood process in terms of the molecules involved. It is driven by different Adaptor Proteins (such as AP2), which directly link the clathrin scaffold to cargo, as well by modulators (like accessory proteins FCHO1/2 and EPS15), which temporarily regulate clathrin-coated vesicle (CCV) assembly and dissassembly. Mutations affecting endocytosis, both in the cargo as well as in the modulators, have been directly linked to cancer. In vivo, AP2 solely interacts with one leaflet of the cellular membrane, therefore, our approach to date has been to build simple, in vitro, experimental models to quantify by Neutron Reflectometry the physical structures formed by AP2 and clathrin on association to planar, cargo-embedded lipid monolayers (article in preparation). This continuation proposal will now focus on the molecular effect of modulators FCHO2 and Eps15 in facilitating conformational activation of AP-2, prior to clathrin binding.
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ZACCAI Nathan; CICUTA Pietro; FAERBER Nicolas; KELLY Bernard; Armando Maestro; MURPHY Leah and OWEN David J.. (2018). Neutron reflectometry studies of clathrin-mediated endocytosis: effect of modulators FCHO/Eps15. Institut Laue-Langevin (ILL) doi:10.5291/ILL-DATA.8-02-829
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