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.

Keywords: nuclear envelope; LINC complex; LEM domain; nuclear envelopathies; cell migration; signal transduction

Figure 1. A schematic illustration depicting the nuclear membranes and examples of known NET proteins. Also shown are the nuclear lamins, nuclear pores and nucleoplasmic factors. BAF – barrier to autointegration factor; GCL – germ cell less; HP1 – heterochromatin protein 1; INM – inner nuclear membrane; IF – intermediate filaments; LAP2 – lamin‐associated protein 2; LBR – lamin B receptor; MT – microtubules; ONM – outer nuclear membrane; pRB – retinoblastoma protein.
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Further Reading

Rothballer A, Schwartz TU and Kutay U (2013) LINCing complex functions at the nuclear envelope: what the molecular architecture of the LINC complex can reveal about its function. Nucleus 4: 29–36.

Schuler E, Lin F and Worman HJ (1994) Characterization of the human gene encoding LBR, an integral protein of the nuclear envelope inner membrane. Journal of Biological Chemistry 269: 11312–11317.

Wilson KL and Foisner R (2010) Lamin‐binding proteins. Cold Spring Harbor Perspectives in Biology 2: a000554.

Zagairy F, Fichtman B and Harel A (2015) The nuclear pore complex and nuclear transport. Encyclopedia of Life Sciences (in press).

Zuela N and Gruenbaum Y (2015) Lamins: organization, dynamics and function. Encyclopedia of Life Sciences. DOI: 10.1002/9780470015902.a0001342.pub3 (Published Online : 16 Feb 2015).

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Zuela, Noam, and Gruenbaum, Yosef(Apr 2015) Nuclear Membranes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0026032]