Nucleocytoplasmic shuttling: a common theme in mechanotransduction

Abstract

Cells sense their mechanical and physical environment through diverse mechanisms, and these interactions specify a wide range of responses including growth, survival, migration and differentiation. Although much work has focused on dissecting the adhesive and structural components of the cell responsible for transducing external mechanical forces into biochemical signalling cascades, only recently have studies begun to examine how mechanical signals are transmitted to the nucleus and activate specific gene expression programmes. One necessary step in these processes is the transport of signalling molecules from the cytoplasm to the nucleus. The SRF (serum-response factor) and YAP (Yes-associated protein)/TAZ (transcriptional co-activator with PDZ-binding motif) pathways are known mediators of this process in multiple cell types, including mesenchymal stem cells, keratinocytes, mammary epithelial cells and smooth muscle cells. In addition, recent evidence suggests a potential role for β-catenin and Smad signalling in mechanotransduction, but further mechanistic studies are needed to prove this hypothesis. As a model system, the epidermis of the skin is one tissue in which nucleocytoplasmic shuttling mediates cellular mechanosensing and is essential for tissue development, homoeostasis and repair. We propose that nuclear translocation is a common element of mechanotransduction conserved across multiple cell types and tissues.