Pathogenic variants in Z-disk structural and signaling proteins, including alpha-actinin, filamin C, and titin, are associated with the development of inherited cardiomyopathies such as HCM and DCM.
This review highlights the critical role of Z-disk proteins in maintaining cardiac structural stability and how their genetic variants contribute to the pathogenesis of inherited cardiomyopathies.
The sarcomere is the smallest functional unit of muscle contraction. It is delineated by a protein-rich structure known as the Z-disk, alternating with M-bands. The Z-disk anchors the actin-rich thin filaments and plays a crucial role in maintaining the mechanical stability of the cardiac muscle. A multitude of proteins interact with each other at the Z-disk and they regulate the mechanical properties of the thin filaments. Over the past 2 decades, the role of the Z-disk in cardiac muscle contraction has been assessed widely, however, the impact of genetic variants in Z-disk proteins has still not been fully elucidated. This review discusses the various Z-disk proteins (alpha-actinin, filamin C, titin, muscle LIM protein, telethonin, myopalladin, nebulette, and nexilin) and Z-disk-associated proteins (desmin, and obscurin) and their role in cardiac structural stability and intracellular signaling. This review further explores how genetic variants of Z-disk proteins are linked to inherited cardiac conditions termed cardiomyopathies.
Noureddine et al. (Thu,) conducted a review in Cardiomyopathies. Pathogenic variants in Z-disk structural and signaling proteins, including alpha-actinin, filamin C, and titin, are associated with the development of inherited cardiomyopathies such as HCM and DCM.