Structures of EHD2 filaments on curved membranes provide a model for caveolar neck stabilization

Abstract

Abstract Caveolae are flask-shaped invaginations of the plasma membrane serving critical functions in mechano-protection and signal transduction. Caveolar dynamics, such as caveolar movement within the plasma membrane or endocytosis, relies on precise shaping of the highly curved caveolar necks. The dynamin-like EHD2 ATPase is proposed to oligomerize around the caveolar neck, but its detailed molecular action is poorly understood. Here, we employ cryo-electron tomography to elucidate structures of ring-like EHD2 filaments on tubulated liposomes. EHD2 forms highly curved membrane scaffolds which stabilize a tubular membrane geometry with undulations along the tube’s axis, resembling caveolar neck architecture. An amino-terminal sequence facilitates this geometry by acting as a spacer between adjacent filaments. Moreover, in endothelial cells lacking EHD2, caveolar necks become narrower and more elongated. Our structural work provides the molecular framework for understanding EHD2 scaffold formation and its cellular function in caveolar dynamics.