A Tubules-First Model for the Origin of Eukaryotic Membrane Traffic

Abstract

The discovery of membrane trafficking proteins in Asgard archaea-the closest archaeal relatives of eukaryotes-reveals the deep evolutionary roots of the eukaryotic endomembrane system. This review synthesizes genomic, structural, and functional studies of archaea and eukaryotes to explore how these ancient proteins contributed to the emergence of intracellular membranes. While Asgard archaea appear to lack the canonical machinery for coated vesicle formation, they encode a full complement of proteins involved in membrane tubulation, scission, tethering, and fusion. This molecular repertoire suggests that the archaeal ancestor of eukaryotes was capable of membrane remodeling, potentially via transient tubules. In early eukaryotes-following mitochondrial acquisition and internalization of the endoplasmic reticulum-tubules may have served as the principal carriers of membrane traffic. Coated vesicles-spherical vesicles that use scaffold proteins and sterol-rich membranes to stabilize high-curvature buds-may represent a later innovation prior to the last eukaryotic common ancestor. Archaea-derived tubular trafficking pathways play essential roles in modern eukaryotic cells.