Characterization of skeletal muscle in the synemin knock-out mouse

García‐Pelagio, Karla P.; Muriel, Joaquin M.; Lovering, Richard M.; Lund, Linda M.; Bond, Meredith; Bloch, Robert J.

doi:10.1063/1.4901362

Cited by 1 publication

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References 21 publications

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“…Experiments were done at 8°C, controlled by a thermistor connected to a temperature controller (Yellow Springs Instrument, Ohio, OH), which maintained the temperature through a two Peltier modulus system (Midland Ross, Cambridge, MA). Tension of the whole system, ␥total, the maximal tension sustained by the costameres, ␥costameres, and the maximal sarcolemmal tension ␥sarcolemma (all measured in dyn/cm), were estimated using the Young-Laplace equation as previously described (29,31,75). The SLs studied were longer than optimal length to eliminate the contribution of invaginations and caveolae at SLs Ͻ3 m (22).…”

Section: Methodsmentioning

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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