Figure 1.

The archetypal SUN-KASH domain association in the LINC complex. (a) The LINC complex is typified by an association between SUN-domain proteins (yellow) on the inner nuclear membrane and KASH-domain proteins (green, blue, and orange) on the outer nuclear membrane. KASH-domain proteins form a functional link with the networks of cytoplasmic intermediate filaments, microtubules, and actin microfilaments, which compose the cytoskeleton. SUN-domain proteins bind to the nuclear lamina, a network of intermediate filaments composed of varying isoforms of A- and B-type lamins, LAPs, and LRs. The lamina also serves as a tethering point for the genome, with associations reported among various lamins, LAPs, and LRs. (b) KASH domains associate with SUN domains in the perinuclear space, and this association maintains the architecture of the nuclear envelope. SUN proteins can associate promiscuously with KASH proteins and can also form homo- and heterodimers with other SUN proteins. (c) Two competing models explain the 3D organization of CTs in the interphase nucleus. The CT-IC model posits that a largely DNA-free compartment of contiguous spaces between adjacent CTs exists. The second model, known as the intermingling model, maintains that whereas CTs occupy nonrandom spaces in the interphase nucleus, there is a large amount of intermingling of the chromatin between adjacent CTs. Abbreviations: CT, chromosome territory; IC, interchromsomal compartment; KASH, Klarsicht/ANC-1/Syne-1 homology; LAP, lamin-associated protein; LINC, linker of the nucleoskeleton and cytoskeleton; LR, lamin receptor; NPC, Nuclear Pore Complex; SUN, Sad1 and UNC84.