Life outside the LINC complex - Do SUN proteins have LINC-independent functions?

Sad1 and UNC84 (SUN) and Klarsicht, ANC-1, and Syne homology (KASH) proteins interact at the nuclear periphery to form the linker of nucleoskeleton and cytoskeleton (LINC) complex, spanning the nuclear envelope (NE) and connecting the cytoskeleton with the nuclear interior. It is now well-documented that several cellular functions depend on LINC complex formation, including cell differentiation and migration. Intriguingly, recent studies suggest that SUN proteins participate in cellular processes where their association with KASH proteins may not be required.

SUN2 regulates mitotic duration in response to extracellular matrix rigidity.

How cells adjust their growth to the spatial and mechanical constraints of their surrounding environment is central to many aspects of biology. Here, we examined how extracellular matrix (ECM) rigidity affects cell division. We found that cells divide more rapidly when cultured on rigid substrates.

Analyzing Mechanotransduction Through the LINC Complex in Isolated Nuclei.

The mechanical properties of the cellular microenvironment can impact many aspects of cell behavior, including molecular processes in the nucleus. Recent studies indicate that the LINC complex and its associated nuclear envelope transmit and transduce mechanical stress into biochemical pathways that ultimately regulate nuclear structure or gene expression. Here we describe a method to apply tensional forces to the LINC complex of isolated nuclei.

Mechanotransduction via the nuclear envelope: a distant reflection of the cell surface.

As the largest and stiffest organelle in the cell, the nucleus can be subjected to significant forces generated by the cytoskeleton to adjust its shape and position, and accommodate the cellular machinery during cell migration, differentiation or division. As it was anticipated, recent work showed that mechanosensitive mechanisms exist in the nucleus and regulate its structure and function in response to mechanical force. While the molecular mechanisms that mediate this response are only beginning to be elucidated, the nuclear envelope seems to play a central role in this process.

Under Pressure: Mechanical Stress Management in the Nucleus.

Cells are constantly adjusting to the mechanical properties of their surroundings, operating a complex mechanochemical feedback, which hinges on mechanotransduction mechanisms. Whereas adhesion structures have been shown to play a central role in mechanotransduction, it now emerges that the nucleus may act as a mechanosensitive structure. Here, we review recent advances demonstrating that mechanical stress emanating from the cytoskeleton can activate pathways in the nucleus which eventually impact both its structure and the transcriptional machinery.