Abstract
Sarcomere assembly and maintenance are essential physiological processes required for cardiac and skeletal muscle function and organism mobility. Over decades of research, components of the sarcomere and factors involved in the formation and maintenance of this contractile unit have been identified. Although we have a general understanding of sarcomere assembly and maintenance, much less is known about the development of the thin filaments and associated factors within the sarcomere. In the last decade, advancements in medical intervention and genome sequencing have uncovered patients with novel mutations in sarcomere thin filaments. Pairing this sequencing with reverse genetics and the ability to generate patient avatars in model organisms has begun to deepen our understanding of sarcomere thin filament development. In this review, we provide a summary of recent findings regarding sarcomere assembly, maintenance, and disease with respect to thin filaments, building on the previous knowledge in the field. We highlight debated and unknown areas within these processes to clearly define open research questions.
Highlights
Striated muscle requires the coordination of hundreds of proteins for cellular function and for assembly of the contractile sarcomere units within the myofibril.While the assembly and maintenance of myosin thick filaments and titin within the sarcomere have been the spotlight of many studies in muscle development and myopathies, the formation and maintenance of the thin filaments have been largely under-characterized despite the suite of myopathies originating from components of thin filament development
Sarcomere thin filament assembly and maintenance is highly conserved across striated muscle with a few isoform and tissue-specific exceptions
While no chaperones have been identified for nebulin folding, NRAP, KLHL41, and KLHL40 bind to nebulin and prevent the giant from aggregating or degrading [23,24,25,26]
Summary
Striated muscle requires the coordination of hundreds of proteins for cellular function and for assembly of the contractile sarcomere units within the myofibril. The purpose of this review is to present the discoveries of thin filament assembly and maintenance in the last decade. We will combine these findings with previous knowledge of thin filament development to highlight a model for thin filament assembly/maintenance and how this relates to muscle disease. Sarcomere thin filament assembly and maintenance is highly conserved across striated muscle with a few isoform and tissue-specific exceptions. We discuss these cardiac and skeletal sarcomere thin filament differences in the appropriate sections below
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