Actin from within - how nuclear myosins and actin regulate nuclear architecture and mechanics.

Abstract

Over the past two decades, significant progress has been made in understanding mechanotransduction to the nucleus. Nevertheless, most research has focused on outside-in signalling orchestrated by external mechanical stimuli. Emerging evidence highlights the importance of intrinsic nuclear mechanisms in the mechanoresponse. The discovery of actin and associated motor proteins, such as myosins, in the nucleus, along with advances in chromatin organisation research, has raised new questions about the contribution of intranuclear architecture and mechanics. Nuclear actin and myosins are present in various compartments of the nucleus, particularly at sites of DNA processing and modification. These proteins can function as hubs and scaffolds, cross-linking distant chromatin regions and thereby impacting local and global nuclear membrane shape. Importantly, nuclear myosins are force-sensitive and nuclear actin cooperates with mechanosensors, suggesting a multi-level contribution to nuclear mechanics. The crosstalk between nuclear myosins and actin has significant implications for cell mechanical plasticity and the prevention of pathological conditions. Here, we review the recent impactful findings that highlight the roles of nuclear actin and myosins in nuclear organisation. Additionally, we discuss potential links between these proteins and emphasize the importance of using new methodologies to unravel nuclear-derived regulatory mechanisms distinct from the cytoskeleton.