An unresolved LINC in the nuclear envelope

Abstract

The nuclear envelope segregates the nucleoplasm from the cytoplasm and is a key feature of eukaryotic cells. Nuclear envelope architecture is comprised of two concentric membrane shells which fuse at multiple sites and yet maintain a uniform separation of 30-50 nm over the rest of the membrane. Studies have revealed the roles for numerous nuclear proteins in forming and maintaining the architecture of the nuclear envelope. However, there is a lack of consensus on the fundamental forces and physical mechanisms that establish the geometry. The objective of this review is to discuss recent findings in the context of membrane mechanics in an effort to define open questions and possible answers.

Figure 1

Figure shows the outer nuclear membrane (ONM) and the inner nuclear membrane (INM) maintained at 45+/−5 nm (adapted from Chang et al., 2015). The SUN protein is a trimer that is embedded on the N terminal side in the INM and binds to KASH domain containing proteins embedded in the ONM. These link to the cytoskeleton. SUN and KASH proteins have been proposed to be responsible for maintaining the distance at 45 nm, although the mechanism is unclear.

Figure 2

Left: ONM expansion observed in HeLa cells with a disrupted LINC complex [(Crisp et al., 2006)]. Middle: Normal NE spacing in C. elegans nuclei lacking a functional LINC complex [(Cain et al., 2014)]. Right: Increase in NE spacing at the anterior and posterior ends of unc-84 (SUN) mutant muscle cell nuclei [(Cain et al., 2014)].

Figure 3

Spontaneous curvature potentially generated by tethered proteins such as SUN1 due to the entropic repulsion between the coiled domains. The same entropic force can also prevent the bilayers from coming close together for fusion. Blue bubbles represent the excluded volume regions created by fluctuations of free SUN proteins.

Figure 4

The natural tendency of the bilayer to expand out near an existing pore in order to reduce the bending energy. A higher density of LINC complexes near the pores can provide the necessary force to flatten the bilayer.