myomesins

Myomesins are a family of proteins that serve as key structural components of the M-line in the sarcomere, the fundamental contractile unit of striated muscle. Two main isoforms, MYOM1 and MYOM2, are encoded by distinct genes on human chromosomes 6 and 8, respectively. Both isoforms contain an N‑terminal domain that binds to the microtubule‑associated protein MAP6 and a C‑terminal domain that interacts with the Myosin Heavy Chain (MYH) in the sarcomere center.

The primary function of myomesins is to cross‑link myosin filaments, thereby maintaining the integrity and alignment of thick filaments and contributing to the mechanical stability of the sarcomere during contraction and relaxation cycles. Beyond structural roles, myomesins are involved in signaling pathways that regulate muscle differentiation and repair. In particular, phosphorylation of the myomesin tails modulates their binding affinity to myosin and other sarcomeric proteins, affecting sarcomere length and compliance.

Alterations in myomesin expression or structure have been implicated in various myopathies. Cardiomyopathies and skeletal muscle disorders such as nemaline myopathy show dysregulation of MYOM1 and MYOM2 transcripts. Mutations within the binding domains can disrupt sarcomere assembly, leading to compromised muscle function. Recent studies using CRISPR‑mediated knockouts in mouse models have highlighted the essential role of myomesins in cardiac development, with loss of either isoform resulting in arrhythmias and reduced contractile force.

Research continues to uncover additional roles for myomesins, including potential involvement in mechanotransduction and sarcomere remodeling during exercise and disease states. Their conserved domains and critical sarcomeric interactions make myomesins a focal point for therapeutic strategies aimed at strengthening muscle resilience and treating congenital myofibrillar disorders.