Fig. 8: Model for the potential role and mechanism of Sun2 in mediating response of nucleus to mechanical stress in young and senescent cells.
From: Nuclear softening mediated by Sun2 suppression delays mechanical stress-induced cellular senescence
The Linker of nucleoskeleton to cytoskeleton (LINC) complex physically connect the nucleus to the cytoplasm. The nuclear lamina is directly connected to Sun1 and Sun2 on the inner nuclear membrane. Sun proteins penetrate through the intermembrane space and bind nesprins on the outer nuclear membrane, which is connected with cytoskeleton. In the situation of lower mechanical stress, both Sun1 and Sun2 are expressed at a relatively lower level in nucleus; however, in the situation of higher mechanical stress, Sun2 expression is specifically elevated. High Sun2 expression can be coupled with increased actin cytoskeleton assembly, RhoA activation, nuclear stiffness and nuclear blebbing, and accelerated cellular senescence. Our results also demonstrated that suppression of Sun2 in progeria cells is able to promote nuclear decoupling, nucleus softening and reduce mechanical stress-induced nuclear damages, and therefore delay the process of cellular senescence.
