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

Abstract

Caveolae are flask-shaped invaginations of the plasma membrane serving critical functions in mechano-protection and signal transduction. Caveolar dynamics, such as 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 form an oligomeric scaffold around the caveolar neck, but its detailed molecular action is poorly understood. Here, we employed cryo-electron tomography to elucidate structures of EHD2 filaments oligomerized on tubulated liposomes. EHD2 filaments form a highly curved membrane scaffold which stabilizes a sophisticated tubular membrane geometry with undulations along the tubes axis. An amino-terminal sequence facilitates this geometry by inserting into the membrane, thereby acting as a spacer between adjacent filaments. Moreover, in endothelial cells lacking EHD2, caveolar necks become narrower and elongated. Our structural work provides the molecular framework for understanding EHD2 scaffold formation and its cellular function in caveolar dynamics.