Nucleus Mechanosensing in Cardiomyocytes

Abstract

Cardiac muscle contraction is distinct from the contraction of other muscle types. The heart continuously undergoes contraction-relaxation cycles throughout an animal's lifespan. It must respond to constantly varying physical and energetic burdens over the short term on a beat-to-beat basis and relies on different mechanisms over the long term. Muscle contractility is based on actin and myosin interactions that are regulated by cytoplasmic calcium ions. Genetic variants of sarcomeric proteins can lead to the pathophysiological development of cardiac dysfunction. The sarcomere is physically connected to other cytoskeletal components. Actin filaments, microtubules and desmin proteins are responsible for these interactions. Therefore, mechanical as well as biochemical signals from sarcomeric contractions are transmitted to and sensed by other parts of the cardiomyocyte, particularly the nucleus which can respond to these stimuli. Proteins anchored to the nuclear envelope display a broad response which remodels the structure of the nucleus. In this review, we examine the central aspects of mechanotransduction in the cardiomyocyte where the transmission of mechanical signals to the nucleus can result in changes in gene expression and nucleus morphology. The correlation of nucleus sensing and dysfunction of sarcomeric proteins may assist the understanding of a wide range of functional responses in the progress of cardiomyopathic diseases.

Keywords: cardiomyocytes; cardiomyopathy; mechanotransduction.

Figure 1

Schematic of intermediate filaments of desmin interconnected with sarcomeres and nucleus in a cardiomyocyte.

Figure 2

Nuclear envelope and cytoskeleton schematic—Schematic of nucleus’s inner and outer membranes, and nuclear protein interactions with chromatin and cytoskeleton: F-actin, microtubules, and intermediate filaments, showing further connection with the sarcomere. ONM, outer nuclear membrane; INM, inner nuclear membrane; NPC, nuclear pore complex; LAP 1 and 2, lamina-associated polypeptides 1 and 2; LBR, lamin B receptors; BAF, barrier-to-autointegration factor; HP 1, heterochromatin protein 1.