The Nucleoskeleton

Abstract

SUMMARYThe nucleoskeleton is an important structural feature of the metazoan nucleus and is involved in the regulation of genome expression and maintenance. The nuclear lamins are intermediate filament proteins that form a peripheral nucleoskeleton in concert with other lamin-associated proteins. Several other proteins normally found in the cytoskeleton have also been identified in the nucleus, but, as will be discussed here, their roles in forming a nucleoskeleton have not been elucidated. Nevertheless, mutations in lamins and lamin-associated proteins cause a spectrum of diseases, making them interesting targets for future research.

Figure 1.

Schematic diagram of the nucleoskeleton and its relationships to the nuclear envelope and cytoskeleton. The proposed major components of the vertebrate nucleoskeleton are illustrated. The lamina comprises polymers of A- and B-type lamins. A fraction of lamins are also present in the nuclear interior, possibly associated with chromatin, but not demonstrably in a polymerized form. Short filaments of actin are illustrated, although monomeric actin might also be present. Nuclear spectrin is indicated as associated primarily with the nuclear envelope/lamina. A nuclear isoform of titin also occurs in most eukaryotic cell nuclei and associates with both chromosomes and the lamina. Pore-linked filaments (PLFs) associated with nuclear pore complexes (NPCs) might interact with chromatin and other nucleoskeletal components. The nucleoskeleton is linked to the cytoplasmic skeletal components through LINC (links the nucleoskeleton and cytoskeleton) complexes comprising SUN (Sad1p–UNC-84)-domain proteins and nesprins (nuclear envelope spectrin-repeat proteins). NM, nuclear membrane (nuclear envelope).

Figure 2.

Carboxy-terminal processing of lamins. The flow diagram illustrates the sequential processing steps necessary to convert prelamin A, prelamin B1, and prelamin B2 to mature proteins. Each successive step requires the completion of the previous modification. Lamins B1 and B2 do not undergo the final protease cleavage step and remain permanently farnesylated and carboxymethylated. The fate of the 15-amino-acid farnesylated peptide removed from prelamin A is unknown, but the peptide is thought to be degraded.

Figure 3.

Visualization of the lamin meshworks in the lamina of mouse embryo fibroblasts. Lamin A (LA) and lamin B1 (LB1) were detected by indirect immunofluorescence and visualized using three-dimensional structured illumination microscopy (Shimi et al. 2015). The LA and LB1 proteins form separate structures, seen by the lack of overlap between the red and blue colors. The upper left panel is an image of the bottom surface of a fibroblast nucleus. The white box is magnified in the image to the right, and the contribution of each lamin is shown in the lower two panels. Scale bar, 5 µm. OL, overlay.