Nuclear Membranes

Abstract

The nuclear envelope (NE) is a double membrane barrier that separates the nuclear content from the cytoplasm. The outer nuclear membrane is contiguous with the endoplasmic reticulum (ER). The perinuclear space or lumen separates the nuclear membranes. Both nuclear membranes contain numerous nuclear envelope transmembrane proteins (NETs), many of them are expressed in a tissue‐ and developmental‐specific manner. These proteins are responsible for the majority of the recently discovered NE functions, which include cell migration, chromatin organisation, cell signalling, gene silencing and transcriptional regulation. NETs are also implicated in diseases, collectively known as nuclear envelopathies, affecting bones, skin, muscles, neurons and systemic disorders. The mechanisms leading to these diseases are largely unknown and are major research goals for future studies. Further studies of the nuclear membranes, their proteins and novel functions will help us expand our understanding of their vast array of cellular functions and gain insights into numerous diseases. Key Concepts The nuclear envelope separates the nucleus from the cytoplasm. It is composed of an outer nuclear membrane (ONM), an inner nuclear membrane (INM), nuclear pore complexes (NPCs) and nuclear lamina. The INM is fused to the ONM at the NPC sites. The INM contains a unique set of nuclear envelope transmembrane proteins (NETs), many of which are expressed in a tissue‐specific manner. Many NETs share common protein domains with other NETs including the LEM, SUN and KASH domains. NETs are involved in regulating signalling pathways and gene positioning. Most NETs interact either directly or indirectly with nuclear lamins. SUN‐domain proteins interact in the perinuclear space with KASH‐domain proteins to make the LINC (linker of nucleoplasm and cytoplasm) complexes that physically link the nuclear interior with the cytoplasmic filament networks and organelles. Mutations in several human NETs cause heritable diseases.