A Novel Mechanism of Membrane Fission by Growth of a Membrane-active Polymer

Abstract

Endocytosis and recycling pathways regulate the display of receptors on the plasma membrane. Cells regulate recycling of membrane receptors by sorting them to tubular recycling endosomes. The ATP-binding protein, EHD1 (EPS 15 homology domain-containing protein 1) is known to localize to recycling endosomes. Cells depleted of EHD1 show defective recycling. Our work describes the membrane-active functions of this protein. We show that ATP-binding is necessary for membrane recruitment and modulates its distribution in cells. EHD1 displays preferential binding to highly curved membranes tubes, and bulges the underlying membrane. ATP hydrolysis promotes self-assembly of the polymer which triggers extensive membrane remodeling of membrane tube, leading to fission. Deletion of N-terminal residues of EHD1 causes a defect in bulge expansion and membrane fission. Comparing EHD1 to a closely related paralog, EHD2, we show at that EHD2 has a slower ATPase activity and is less effective in membrane remodeling