Structural and Functional Roles of Desmin in Mouse Skeletal Muscle during Passive Deformation

Shah, Sameer B.; Davis, Jennifer; Weisleder, Noah; Kostavassili, Ioanna; McCulloch, Andrew D.; Ralston, Evelyn; Capetanaki, Yassemi; Lieber, Richard L.

doi:10.1016/s0006-3495(04)74349-0

Cited by 123 publications

(140 citation statements)

References 64 publications

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“…This assumption originated before the identification of the elastic protein titin, which binds the Z-to the M-line. Furthermore, desmin knock-out muscles show the same passive elastic properties as control muscles (59).…”

Section: Putative Functionsmentioning

confidence: 80%

Desmin: molecular interactions and putative functions of the muscle intermediate filament protein

Costa

Escaleira

Cataldo

et al. 2004

Braz J Med Biol Res

121

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Desmin is the intermediate filament (IF) protein occurring exclusively in muscle and endothelial cells. There are other IF proteins in muscle such as nestin, peripherin, and vimentin, besides the ubiquitous lamins, but they are not unique to muscle. Desmin was purified in 1977, the desmin gene was characterized in 1989, and knock-out animals were generated in 1996. Several isoforms have been described. Desmin IFs are present throughout smooth, cardiac and skeletal muscle cells, but can be more concentrated in some particular structures, such as dense bodies, around the nuclei, around the Z-line or in costameres. Desmin is up-regulated in muscle-derived cellular adaptations, including conductive fibers in the heart, electric organs, some myopathies, and experimental treatments with drugs that induce muscle degeneration, like phorbol esters. Many molecules have been reported to associate with desmin, such as other IF proteins (including members of the membrane dystroglycan complex), nebulin, the actin and tubulin binding protein plectin, the molecular motor dynein, the gene regulatory protein MyoD, DNA, the chaperone αB-crystallin, and proteases such as calpain and caspase. Desmin has an important medical role, since it is used as a marker of tumors' origin. More recently, several myopathies have been described, with accumulation of desmin deposits. Yet, after almost 30 years since its identification, the function of desmin is still unclear. Suggested functions include myofibrillogenesis, mechanical support for the muscle, mitochondrial localization, gene expression regulation, and intracellular signaling. This review focuses on the biochemical interactions of desmin, with a discussion of its putative functions.

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Section: Putative Functionsmentioning

confidence: 80%

Desmin: molecular interactions and putative functions of the muscle intermediate filament protein

Costa

Escaleira

Cataldo

et al. 2004

Braz J Med Biol Res

121

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“…IFs, composed of desmin, synemin, and keratins (16,86), are considered to be mediators of mechanical stress and force transduction in striated muscle (36,47). The major IF protein is desmin, which surrounds the contractile apparatus at Z disks and serves as an important linkage to costameres at the sarcolemma (16).…”

Section: Discussionmentioning

confidence: 99%

“…Mutations in the lamins are associated with Emery-Dreifuss and Limb-girdle muscular dystrophy type 1B (60). Nestin (type VI) plays a role in the accumulation of acetylcholine receptors at the neuromuscular junction and in the development of myogenic cells (86,94). Muscles lacking keratin 19 (type I) or desmin (type III) are mildly myopathic and are weaker and more easily injured than wild-type (WT) (1,54,88).…”

mentioning

confidence: 99%

Myopathic changes in murine skeletal muscle lacking synemin

García‐Pelagio

Muriel

O’Neill

et al. 2015

American Journal of Physiology-Cell Physiology

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(IF) proteins are associated with defects in the organization of the contractile apparatus and its links to costameres, which connect the sarcomeres to the cell membrane. Here we study the role in skeletal muscle of synemin, a type IV IF protein, by examining mice null for synemin (synm-null). Synm-null mice have a mild skeletal muscle phenotype. Tibialis anterior (TA) muscles show a significant decrease in mean fiber diameter, a decrease in twitch and tetanic force, and an increase in susceptibility to injury caused by lengthening contractions. Organization of proteins associated with the contractile apparatus and costameres is not significantly altered in the synm-null. Elastimetry of the sarcolemma and associated contractile apparatus in extensor digitorum longus myofibers reveals a reduction in tension consistent with an increase in sarcolemmal deformability. Although fatigue after repeated isometric contractions is more marked in TA muscles of synm-null mice, the ability of the mice to run uphill on a treadmill is similar to controls. Our results suggest that synemin contributes to linkage between costameres and the contractile apparatus and that the absence of synemin results in decreased fiber size and increased sarcolemmal deformability and susceptibility to injury. Thus synemin plays a moderate but distinct role in fast twitch skeletal muscle. cytoskeleton; costameres; elastimetry; biomechanical properties; desmin A LARGE NUMBER OF HUMAN DISEASES, ranging from skin disorders (51), to premature aging (34, 64), to skeletal and cardiac myopathies (19,37), are linked to mutations in genes encoding intermediate filament (IF) proteins (25). Since the discovery of desmin, the major IF protein of striated muscle (49), its role and that of other IF proteins in muscle have been of keen interest to many laboratories (reviewed in 16). Our research on muscle IF proteins has addressed their role in force transmission and in organizing the sarcoplasm and stabilizing it against injury during force generation.Force generated in muscle can be transmitted radially, from the myofibrils, across the sarcolemma to the extracellular matrix and neighboring cells (11, 67). As a result, a significant amount of force is exerted on the sarcolemma and the structures that link it to the underlying contractile apparatus and the extracellular matrix. The ability of the sarcolemma with the underlying contractile apparatus to withstand the distortions caused during isotonic contractions (2, 11, 12) depends on specialized structures, termed "costameres" (66), that mediate the radial transmission of force across the sarcolemma (11). Costameres are structures at the sarcolemma of striated muscle fibers that align circumferentially around the Z disks and the M bands of the nearest myofibrils, and longitudinally, to form a rectilinear sarcolemmal network comprised of integral membrane proteins (such as dystroglycan, the sarcoglycans, and Na-K-ATPase), proteins of the extracellular matrix (such as laminin and collagen IV), and proteins of t...

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“…A reduced desmin in tamoxifenadministered mice might point to a perturbation or dysfunction of the myofibers, leading to the weakness of its tensile strength and disruption with the resultant abnormal architecture. In skeletal muscles, desmin is essential for the tensile strength and integrity of myofibrils but not for myogenic commitment, differentiation, and fusion (Milner et al 1996, Park et al 2000, Shah et al 2004.…”

Section: Controlmentioning

confidence: 99%

The effects of tamoxifen and estradiol on myometrial differentiation and organization during early uterine development in the CD1 mouse

Mehasseb

Bell²,

Habiba³

2009

Reproduction

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We used a neonatal mouse model to examine the histogenesis of uterine adenomyosis, and to test whether adenomyosis is due to an abnormality in myometrial differentiation, or in extracellular matrix proteins expression. We also studied the effects of tamoxifen and estradiol on uterine development, myometrial differentiation, and organization. Female CD1 pups were treated with oral tamoxifen (1 mg/kg) (nZ27) or estradiol (0.1 mg/kg) (nZ24) from age 1 to 5 days. Uteri from control (nZ27) and treated mice were obtained on days 2, 5, 10, 15, and 42 of age. We examined the sections histologically, using image analysis and immunohistochemistry for a-smooth muscle actin (a-SMA), desmin, vimentin, laminin, fibronectin, and estrogen receptor-a. Following tamoxifen exposure, all uteri showed adenomyosis by 6 weeks of age (seen as early as day 10). The inner myometrium showed thinning, lack of continuity, disorganization, and bundling. a-SMA expression was normal. Desmin expression normally showed a wave of maturation that was absent in tamoxifen-treated mice. In the estradiol group, adenomyosis was not observed. All uterine layers were normally developed, but hypertrophied. The inner myometrium retained its circular arrangement. There was no difference in the localization of laminin or fibronectin between groups (laminin expression was reduced in the tamoxifen treated uteri). Vimentin could not be detected in all groups. Our results suggest that the development of the inner myometrium is particularly sensitive to estrogen antagonism, and can be affected by steroid receptors modulation. Disruption of the inner myometrium may play a role in the development of uterine adenomyosis.

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Structural and Functional Roles of Desmin in Mouse Skeletal Muscle during Passive Deformation

Cited by 123 publications

References 64 publications

Desmin: molecular interactions and putative functions of the muscle intermediate filament protein

Desmin: molecular interactions and putative functions of the muscle intermediate filament protein

Myopathic changes in murine skeletal muscle lacking synemin

The effects of tamoxifen and estradiol on myometrial differentiation and organization during early uterine development in the CD1 mouse

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