Topology of membrane compartments

Ordinary vesicle budding and fusion preserve which side of a membrane a protein domain faces: a cytoplasmic domain remains cytoplasmic, and a luminal domain remains luminal. Invagination can enclose previously external space without transporting its contents through a bilayer. The endoplasmic reticulum lumen is continuous with the space between the two nuclear envelope membranes; it is not the chromosome-containing nucleoplasm. Any proposed evolutionary remodelling must account for these distinct spaces and the membrane connections between them.