[4] The KASH family of proteins is a major component of the LINC complex, totaling six members and ultimately engaging with all aspects of the cytoskeleton.
While the exact mechanism is not yet fully understood, it is speculated that a dense network of lamin A/C controls the access to heterochromatin and transcription factor localization.
[4] Mechanotransduction has been established as the ability of the nucleus to sense mechanical forces which triggers a biological response, converting the initial stimulus into some form of electrochemical activity.
This phenomenon can be evoked through a multitude of mechanical pathways, including compression, shear stresses, osmotic changes, cell adhesions, vibrational stimuli and intracellular generated forces.
Nuclear stiffening is one particular response controlled by LINC complex interaction, which was found to be initiated through the actin-binding nesprin -1 in the cytoskeleton.
Stretching nesprin -1 triggers a rapid phosphorylation of emerin, located at the inner nuclear membrane, which alters lamin A and begins a downstream transcription cascade of mechanically regulated genes.
Similarly, work from the Driscoll laboratory demonstrated that the import of YAP under strain of the nucleus is hindered if the LINC complex is disrupted via knockdown of nesprin -1 giant.