Figure 6

Role of Sun-domain and KASH-domain proteins in nuclear envelope architecture. Sun-domain proteins embedded in the inner membrane attach it directly to the DNA surface of the peripheral heterochromatin (the nucleoskeleton). Their Sun-domains (yellow) bind to the KASH domains (purple) of proteins embedded in the outer membrane, which attach it to the cytoplasmic actin filaments, microtubules, and centrosome of the cytoskeleton. Grey pentagons represent the membrane spanning domain(s) of the KASH-domain proteins and grey rods their flexible cytoskeleton-binding N-terminal domains, which differ greatly among the various types. Microtubules may be attached to KASH-domain proteins either by kinesin or dynein motors. The firm Sun-KASH linker complex (known as LINC) within the perinuclear cisterna holds the inner and outer membrane domains of the NE together with the correct spacing and transmits mechanical forces from cytoskeleton to nucleoskeleton or vice versa without damaging it. Some eukaryotes, e.g. animals, lobose amoebae and peridinean dinoflagellates, (probably polyphyletically) evolved a proteinaceous lamina beneath the inner membrane to further strengthen the nuclear periphery, but this was probably absent in the first eukaryotes; additionally to the universal interactions shown, in animals only cytoplasmic intermediate filaments (IF) attach to KASH proteins via plectin adaptors and lamin IF proteins associate with the intranuclear domain of Sun proteins. For simplicity the fact that Sun-domain proteins are homodimers with a coiled coil domain between their two membrane-spanning and chromatin binding domains (lumped here as grey rectangles) and two Sun domains is not depicted.