Abstract
‘All these years that I'm painfully counting The few, the many, the unknown Wandering alone Shining my light in front of a magical mirror’ ( The Guard and the King , Socratis Malamas) How is the ‘identity’ of the nuclear envelope established and what does this structure do, apart from separating the cytoplasm from the nucleoplasm? Touching on these questions, I discuss here the molecular features and the nearest‐neighbour relationships of five integral proteins that represent major components of the inner nuclear membrane. As it turns out, these proteins are organized in large, multi‐subunit complexes, which anchor at the nuclear lamina and ‘trap’ in situ a variety of regulatory factors. It is these factors that impart domain specificity and give the nuclear envelope its unique characteristics. ### Substructure of the nuclear envelope and relationship with the endoplasmic reticulum The nuclear envelope is a modular structure, consisting of discrete, flattened cisternae. These cisternae comprise two different ‘unit membranes’: the outer nuclear membrane, which faces the cytoplasm and is continuous with the rough endoplasmic reticulum (ER); and the inner nuclear membrane, which faces the nucleoplasm and is covered by the nuclear lamina. The inner and outer membranes are separated by a narrow lumen (perinuclear space) and join periodically at the pore membrane. This is a highly specialized membrane domain, exposed on both sides of the cytoplasm–nucleoplasm interface and accommodating the nuclear pore complex. The physico‐chemical properties of the nuclear membranes have not been directly determined. Nevertheless, several studies have been made using intact nuclei and nuclei lacking large pieces of the outer nuclear membrane (e.g. Schindler et al ., 1985). From these experiments it has been inferred that the inner and outer membranes do not differ significantly, having essentially the same phospholipid mobility and lipid composition. A structural relatedness between the nuclear envelope and the ER membrane has been suggested by recent observations, showing that nuclear …