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

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Item Type:Article
Title:Structures of EHD2 filaments on curved membranes provide a model for caveolar neck stabilization
Creators: Vázquez-Sarandeses, Elena ORCID logoORCID: https://orcid.org/0009-0003-3526-7629, Mikirtumov, Vasilii ORCID logoORCID: https://orcid.org/0009-0004-6849-4825, Noel, Jeffrey K. ORCID logoORCID: https://orcid.org/0000-0003-3168-6036, Kudryashev, Mikhail ORCID logoORCID: https://orcid.org/0000-0003-3550-6274 and Daumke, Oliver ORCID logoORCID: https://orcid.org/0000-0002-6190-1414
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.
Keywords:Carrier Proteins, Caveolae, Cell Membrane, Cryoelectron Microscopy, Electron Microscope Tomography, Endothelial Cells, Liposomes, Animals
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group
Volume:17
Number:1
Page Range:7621
Date:31 July 2026
Official Publication:https://doi.org/10.1038/s41467-026-76288-8
PubMed:View item in PubMed
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