LINC Complex in Mechanobiology: Role of Nesprin 4 in Secretory Epithelial Cells

LINC complex proteins connect the nucleoskeleton to the cytoskeleton, which is an important link for processes such as maintaining epithelial cell polarization and mechanobiology. Nesprin 4 (Nesp4), a member of the LINC complex family, is known to play a role in the apical-basal polarization of epithelial cells. The major phenotype for the loss of Nesp4 in mice is hearing loss. Nevertheless, other symptoms including emphysema and reduced lean mass were also observed, which led us to speculate that Nesp4 may have important roles in other tissues such as lungs and pancreas. We show that Nesp4 is indeed expressed in the airway epithelium and show that the expression is restricted to a small population of cells, which are consistent with FOXJ1 positive ciliated cells. These cells are important for mucus secretion and movement in the airways. For pancreatic cells our results suggest that Nesp4 is important for the pancreatic exocrine function and highlight Mist1and TCF7L2 as possible transcriptional regulators of SYNE4 gene expression. Breast tissue is another major site of Nesp4 expression. For breast cancer, defects in cell polarity are associated with cancer cell migration and invasion ability. Our findings show that Nesp4 downregulation coincides with increased motility and cell invasion ability in breast cancer cell lines, which highlights a possible protective role of Nesp4 against breast cancer cells metastasis. Finally, studying of certain mechanobiological aspects of the LINC complex requires specific tools that can apply controlled strain on cells, such as cell stretchers. We have also fully characterized and optimized a cell stretcher suitable for mechanobiological studies.