The LINC complex (Linker of Nucleoskeleton and Cytoskeleton) is a protein complex that spans the nuclear envelope in eukaryotic cells. It consists of nesprins (nuclear envelope spectrin repeat proteins) and SUN proteins (Sad1p/Unc-84 domain proteins). The SUN proteins have a conserved SUN domain that extends into the nucleoplasm and interacts with various nuclear components, including chromatin and nuclear lamins. On the other hand, KASH proteins interact with the cytoskeleton components including actin filaments, microtubules and intermediate filaments.
The LINC complex plays a critical role in providing a structural link between the nucleus and the cytoplasm. This connection is important for various cellular processes such as nuclear positioning and migration, maintaining nuclear shape, force transmission, and mechanotransduction.
While there are several KASH domain proteins, including four Nesprin proteins (Nesprin-1 through Nesprin-4), Sun1 and Sun2 are the two SUN domain proteins expressed in somatic cells. Thus, loss of both Sun1 and Sun2 leads to loss of all LINC complexes in cells. The constitutive loss of SUN1/2 is embryonic lethal. In order to understand the role of these proteins in the skin, we generated a conditional inducible SUN 1/2 dKO. Intriguingly, the adult skin seems to develop quite normally in the absence of the LINC complex. Using the inducible system we also generated SUNdKO embryos and isolated primary keratinocytes. In this talk, I will discuss some unexpected findings of our analysis of the SUN dKO adult skin, embryonic skin and keratinocytes.