Abstract
Mechanically induced signal transduction has an essential role in development. Cells actively transduce and respond to mechanical signals and their internal architecture must manage the associated forces while also being dynamically responsive. With unique assembly-disassembly dynamics and physical properties, cytoplasmic intermediate filaments play an important role in regulating cell shape and mechanical integrity. While this function has been recognized and appreciated for more than 30 years, continually emerging data also demonstrate important roles of intermediate filaments in cell signal transduction. In this review, with a particular focus on keratins and vimentin, the relationship between the physical state of intermediate filaments and their role in mechanotransduction signaling is illustrated through a survey of current literature. Association with adhesion receptors such as cadherins and integrins provides a critical interface through which intermediate filaments are exposed to forces from a cell's environment. As a consequence, these cytoskeletal networks are posttranslationally modified, remodeled and reorganized with direct impacts on local signal transduction events and cell migratory behaviors important to development. We propose that intermediate filaments provide an opportune platform for cells to both cope with mechanical forces and modulate signal transduction.
Highlights
The last decade has brought a newfound recognition for the role of physical force on stimulating adhesion responses in cells, activating signal transduction pathways, and regulating cellular functions
Since the actomyosin machinery is seen as the primary means by which cells generate force, the focus of the research community far has largely been on the tripartite relationship between actin-myosin cytoskeleton, physical parameters such as force, and associated signal transduction pathways
We provide a summary overview of what is currently known about cytoplasmic intermediate filaments and their regulation
Summary
The last decade has brought a newfound recognition for the role of physical force on stimulating adhesion responses in cells, activating signal transduction pathways, and regulating cellular functions. Since the actomyosin machinery is seen as the primary means by which cells generate force, the focus of the research community far has largely been on the tripartite relationship between actin-myosin cytoskeleton, physical parameters such as force, and associated signal transduction pathways. It is well-accepted that the intermediate filaments provide mechanical integrity to cells, the relationship of intermediate filaments to mechanotransduction processes continues to be a new frontier ripe for exploration. Findings to date provide good reason to anticipate an integral role for intermediate filaments in cellular processes where signal transduction and cellular mechanics converge
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