Structural and signaling proteins in the Z-disk and their role in cardiomyopathies

Maya Noureddine; Katja Gehmlich

doi:10.3389/fphys.2023.1143858

Structural and signaling proteins in the Z-disk and their role in cardiomyopathies

Front Physiol. 2023 Mar 2:14:1143858. doi: 10.3389/fphys.2023.1143858. eCollection 2023.

Authors

Maya Noureddine¹, Katja Gehmlich^{1

2}

Affiliations

¹ Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
² Cardiovascular Medicine, Radcliffe Department of Medicine and British Heart Foundation Centre of Research Excellence Oxford, University of Oxford, Oxford, United Kingdom.

Abstract

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.

Keywords: Z-disk protein; alpha-actinin; cardiomyopathy; desmin (DES); filamin C (FLNC); myopalladin (MYPN); pathogenic variant; titin (TTN).

Publication types

Review

Grants and funding

This work is supported by the Advanced Inter-Disciplinary Models (AIM) Doctoral Training Partnership (DTP) funded by the Medical Research Council (MR/W007002/1) to KG and MN KG is supported by the Medical Research Council (MR/V009540/1). The Institute of Cardiovascular Sciences, University of Birmingham, has received an Accelerator Award by the British Heart Foundation (AA/18/2/34218).