Review
Desmin: a major intermediate filament protein essential for the structural integrity and function of muscle

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Abstract

Desmin is a muscle-specific protein and a key subunit of the intermediate filament in cardiac, skeletal and smooth muscles. Desmin filaments are mainly located at the periphery of Z-disk of striated muscles and at the dense bodies of smooth muscle cells, and they have been postulated to play a critical role in the maintenance of structural and mechanical integrity of the contractile apparatus in muscle tissues. This review summarizes the findings in the regulation of the desmin gene and function of the desmin protein. The expression of desmin gene is regulated by a combination of different transcription control regions in muscle cells. The results from mice deficient in desmin reveal the fundamental role of desmin filaments in cell architecture, force transmission and mitochondrial function. Mice lacking desmin postnatally develop a dilated cardiomyopathy, a skeletal myopathy and smooth muscle defects. Some of desmin-related myopathies are attributable to a missense mutations and deletions in the desmin gene. Other desmin-related myopathies, in which the desmin gene is not mutated, could be related to mutations of the genes encoding the proteins that interact with desmin.

Introduction

Muscle cells contain several intermediate filament (IF) proteins, including desmin, vimentin, nestin, synemin, syncoilin, lamins, and cytokeratins [1]. However, desmin is the major muscle-specific IF protein. This 53-kDa type III IF protein is found mainly in the Z-disk of striated muscles and in the dense bodies of smooth muscle cells (SMC). It plays an essential role in maintaining muscle cytoarchitecture by forming a three-dimensional scaffold around the myofibrillar Z-disk and by connecting the entire contractile apparatus to the subsarcolemmal cytoskeleton, the nuclei, and other organelles [2], [3]. Desmin also forms longitudinal connections between the peripheries of successive Z-disks and along the plasma membranes of striated muscle cells. It is particularly abundant at the myotendinous junctions and at the neuromuscular junctions of skeletal muscle, and in the intercalated disks, the attachment between cardiomyocytes in cardiac muscle. There is more desmin in the heart muscle cells (2% of total protein) of mammals than in the skeletal muscle cells (0.35%). And the concentration of desmin in vascular SMC varies with their position in the arterial tree, with the desmin content increasing from the elastic aorta, to the muscular mesenteric arteries, and finally the resistance-sized mesenteric microarteries [4]. This report summarizes the regulation of the desmin gene, the function of the protein in muscle tissues, and its involvement in human disease (_Hlt80691914[Fig. 1).

Section snippets

Regulation of the desmin gene by upstream regions and a muscle-specific control region

Desmin is encoded by a single gene in all the species studied to date. This gene has 9 exons and 8 introns. Desmin is the one of the earliest muscle-specific proteins to appear during myogenesis. Its concentration is low in replicating myoblasts and satellite cells, and high in differentiated myotubes. The desmin gene is activated as early as embryonic day 7.5 in the precardiac area and on day 9 in the myotomes and the smooth muscle cells of the mouse embryo. The regulations of human, mouse,

Lack of desmin in mice leads to defects in all types of muscle

Two group have introduced null mutations into the mouse desmin gene by homologous recombination to understand how the desmin IF functions in vivo [12], [13]. The desmin knockout mice (Des−/−) develop normally and are fertile. Neither the early stages of muscle development nor the subsequent maturation of muscle fibers is affected by the absence of desmin. And no anatomical or behavioral defects are apparent at birth. However, after birth, mice lacking desmin suffer from a cardiomyopathy,

Human desmin-related myopathy

Desmin-related myopathies (DRM) have been linked to skeletal and cardiac myopathies in which the desmin filament network is lost and abnormal aggregates of desmin form in muscle fibers (for review, see Ref. [30]). They have also been called desmin protein surplus myopathies or desmin myopathies. The clinical features are heterogenous, with one or more characteristic symptoms, such as skeletal myopathy, cardiomyopathy, respiratory deficiency, neuropathy, and smooth muscle disorders. Some of

Concluding remarks

The studies on mice lacking desmin indicate that desmin is essential for maintaining the structural integrity and function of muscles, although it is not necessary for the early stages of muscle development or the subsequent maturation of muscle fibers. A lack of desmin leads to cardiomyopathy, skeletal myopathy, and dysfunctional smooth muscle. Desmin may be extremely important for the positioning, distribution, and function of mitochondria. Desmin filaments are involved in the generation of

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