Model for the evolution of nuclear pores and cytoplasmic blebs. (A) Membrane protrusions are formed that extend through holes in the cell wall (S-layer, shown in gray) of the eukaryote ancestor. Protrusions could initially have been coated with an S-layer that was later lost. We propose that protrusions gained structural support at their bases from proteins with seven-blade β-propeller domains (homologs of nucleoporins and COPII coatomers), which stabilize positively curved membranes. Additionally, blebs may have been stabilized by an internal cytoskeleton (red), like that provided by microtubules in modern day flagella, and by components of LINC complexes that connect the cell membrane (and underlying structures) to the S-layer (gray). (B) Lateral spreading of the bleb is aided by the movement of LINC proteins to the inner bleb membrane and by the recruitment of a second, outer ring of nuclear pore proteins to stabilize positive curvature outside of the cell wall.