The nuclear envelopathies and human diseases

The nuclear envelope (NE) is a specialized structure composed of two lipid membranes that separate the cytoplasm from the nucleoplasm. The outer nuclear membrane (ONM), studded with ribosomes, is an extension of the rough ER while the inner nuclear membrane (INM) contacts chromatin and the nuclear lamina, a type V intermediate filament that composes the nuclear skeleton [1]. Although the NE encapsulates chromatin, it is not a uniformly closed barrier. Rather, it has several "doors" represented by the nuclear pore complexes (NPC) that allow communication between the nucleus and the cytoplasm [2].The envelope is an anchorage structure for the nuclear architecture. A number of proteins are associated with the NE. They can be categorized into three groups according to their position in the NE (Fig. 1). The first group is the trans-nuclear membrane proteins in the nuclear pore complex (NPC). The second group is the integral nuclear membrane proteins which are embedded in the inner nuclear membrane via transmembrane domains. The functions of this group are less well characterized due to their insolubility; however, some of the better studied moieties in this group include the Lamin B receptor (LBR), the Lamin-associated polypeptides (LAPs), Emerin, MAN-1 and the Sad1-Unc84 (i.e. SUN) domain proteins. The third group of NE-associated proteins include those underlying the nuclear membrane [3]. Thus, a subset of NE-associated proteins composes the filamentous framework which constitutes nuclear structure and can regulate cellular processes. Beyond their mechanical functions, the NE proteins are involved in many nuclear activities such as DNA replication, chromatin segregation, cell cycle progression, gene transcription, and RNA processing [4]. Below, we review in brief recent perspectives on the NE proteins and how their deficiencies impact human diseases.Many human diseases are associated with NE protein defects [5]. For example, a comprehensive proteomic study identified 1