Nuclear Envelope and Lamins: Organization and Dynamics

Jun Liu, Cornell University, Ithaca, New York

Published online: March 2009

DOI: 10.1002/9780470015902.a0001342.pub2

The nuclear envelope (NE) separates the nucleus and the cytoplasm and plays an important role in the maintenance of nuclear structure. The NE undergoes a complex cycle of assembly and disassembly during cell divisions to allow proper segregation of the chromosomes. Recent advances in basic and clinical research, especially in light of a number of human diseases that are collectively called laminopathies (diseases caused by mutations in A-type lamins or lamin-binding proteins), suggest that the NE not only acts as a structural barrier separating the nuclear genome and transcriptional machinery from the cytoplasm, but also serves as a node that integrates the different structural and signalling networks between the nucleus and the cytoplasm.

Key concepts

  • There are three structural components of the nuclear envelope: the outer and inner nuclear membranes, the nuclear pore complexes and the nuclear lamina.
  • The nuclear lamina is mainly composed of type V intermediate filament proteins called lamins, which contain a C-terminal CAAX motif and undergo extensive post-translational processing.
  • Lamins are grouped into A- and B-types based on their sequence homologies, biochemical properties and behaviors during mitosis.
  • Mutations in LMNA, which encodes the A-type lamins, cause multiple distinct diseases that are collectively called laminopathies in humans, including diseases of striated muscle, peripheral neuropathy, lipodystrophy syndromes and premature aging or progeroid syndromes.
  • Lamins exert multiple functions via interacting with various lamin-binding proteins, including an increasing number of proteins located at the inner nuclear membrane that are retained there because of their interactions with lamin.
  • The lamin-binding inner nuclear membrane proteins also function to modulate the output of cell–cell signalling via interacting with transcription factors of different signalling pathways and integrate nuclear and cytoplasmic architecture via the LINC complex (linker of nucleoskeleton and cytoskeleton).
  • The nuclear pore complexes are large protein assemblies that are organized into structures with eightfold rotational symmetry and serve as gated channels that mediate nucleocytoplasmic transport across the nuclear envelope.
  • The nuclear envelope undergoes ordered disassembly and assembly during mitosis.
  • Disassembly of the nuclear envelope during mitosis is caused by the mitotic phosphorylation of nuclear envelope components.
  • Even during interphase, the nuclear envelope is not static.

Keywords: nuclear envelope; nuclear lamina; lamin; nuclear membrane; nuclear pore complex; nucleoporin

Figure 1. Overall organization of the nuclear envelope. The inner and outer nuclear membranes are separated by the perinuclear space and joined by nuclear pore complexes. The nuclear lamina is tightly associated with chromatin as well as the nucleoplasmic face of the inner nuclear membrane. Some selected INM proteins are shown. The LEM domain proteins, LAP1, emerin and MAN1 bind to BAF, whereas LBR binds to HP1. BAF and HP1 are DNA-binding proteins, thus linking the LEM domain proteins and LBR to chromatin. The cytoskeleton associated nesprin proteins interact with the INM proteins SUN1 and SUN2, thus linking the cytoskeleton and the nucleoskeleton. In C. elegans, the SUN protein SUN-1/MTF-1 binds to the KASH protein ZYG-12, which in turn binds the centrosome, linking the centrosome to the NE. ZYG-12 also recruits Dynein, a microtubule motor, to the NE. Similar SUN protein, KASH protein and microtubule interactions have also been reported in Drosophila (Starr, 2007).
Figure 2. Structure of nuclear lamins. (A) Pre-lamins contain a head domain, the central -helical rod domain and a tail domain that includes the NLS, the Ig-fold and the C-terminal CAAX motif. (B) Post-translational processing of pre-lamin A, B1 and B2. The cysteine residue of the CAAX motif is first farnesylated, followed by the cleavage of the AAX motif by an AAX endopeptidase. The cysteine residue is then methylated by a carboxyl methyltransferase. These steps lead to mature lamin B1 and B2. An additional 15 C-terminal residues, including the farnesylated/carboxymethylated cysteine, are cleaved off by Zmpste24/FACE1 in order to produce mature lamin A.
Figure 3. Structure of the nuclear pore complexes. A cross-section diagram of a vertebrate NPC, showing the cytoplasmic, central spike and nuclear rings that span the nuclear envelope. The cytoplasmic filaments extend to the cytoplasmic side, whereas the nuclear filaments form a basket structure that is closed by a distal ring. Some of the nucleoporins are shown in the diagram, with their relative positions depicted.
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 Further Reading
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    Goldman RD, Gruenbaum Y, Moir RD, Shumaker DK and Spann TP (2002) Nuclear lamins: building blocks of nuclear architecture. Genes & Development 16(5): 533–547.
    Gruenbaum Y, Margalit A, Goldman RD, Shumaker DK and Wilson KL (2005) The nuclear lamina comes of age. Nature Reviews: Molecular Cell Biology 6(1): 21–31.

Related Sub-Topics:

Cell Membranes | Cell Compartments and Cellular Organelles | Cell Cycle | Membrane Proteins | Protein Structure
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Article Title: Nuclear Envelope and Lamins: Organization and Dynamics
 
How to Cite close
Liu, Jun(Mar 2009) Nuclear Envelope and Lamins: Organization and Dynamics. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001342.pub2]