Filopodia powered by class X myosin promote fusion of mammalian myoblasts

Skeletal muscle fibers are multinucleated cellular giants formed by the fusion of mononuclear myoblasts. Several molecules involved in myoblast fusion have been discovered, and finger-like projections coincident with myoblast fusion have also been implicated in the fusion process. The role of these cellular projections in muscle cell fusion was investigated herein. We demonstrate that these projections are filopodia generated by class X myosin (Myo10), an unconventional myosin motor protein specialized for filopodia. We further show that Myo10 is highly expressed by differentiating myoblasts, and Myo10 ablation inhibits both filopodia formation and myoblast fusion in vitro. In vivo, Myo10 labels regenerating muscle fibers associated with Duchenne muscular dystrophy and acute muscle injury. In mice, conditional loss of Myo10 from muscle-resident stem cells, known as satellite cells, severely impairs postnatal muscle regeneration. Furthermore, the muscle fusion proteins Myomaker and Myomixer are detected in myoblast filopodia. These data demonstrate that Myo10-driven filopodia facilitate multi-nucleated mammalian muscle formation.

Filopodia powered by class X myosin promote fusion of mammalian myoblasts

Skeletal muscle fibers are multinucleated cellular giants formed by the fusion of mononuclear myoblasts. Several molecules involved in myoblast fusion have been discovered, and finger-like projections coincident with myoblast fusion have also been implicated in the fusion process. The role of these cellular projections in muscle cell fusion was investigated herein. We demonstrate that these projections are filopodia generated by class X myosin (Myo10), an unconventional myosin motor protein specialized for filopodia. We further show that Myo10 is highly expressed by differentiating myoblasts, and Myo10 ablation inhibits both filopodia formation and myoblast fusion in vitro. In vivo, Myo10 labels regenerating muscle fibers associated with Duchenne muscular dystrophy and acute muscle injury. Conditional loss of Myo10 from muscle-resident stem cells, known as satellite cells, severely impairs postnatal muscle regeneration. Furthermore, the muscle fusion proteins Myomaker and Myomixer are detected in myoblast filopodia. These data demonstrate that Myo10-driven filopodia facilitate multi-nucleated mammalian muscle formation.

DEVELOPMENT OF IMMUNOCHROMATOGRAPHIC TEST-SYSTEM FOR TROPONIN I AND ITS APPLICATION FOR CONTROL OF MEAT PRODUCTS

A method for immunochromatographic analysis of troponin I, a marker of muscle tissue in mammals, was proposed for evaluation of the meat products composition. The procedure of sample preparation included extraction by 0.5 M KCl combined with heat treatment. The efficiency of this method in the assessment of mammalian muscle tissues in various meat products was demonstrated.

Mammalian muscle fibers may be simple as well as slow

Squire and Luther consider new evidence for a simple lattice structure in mammalian skeletal muscle.

Amphiphysin 2 modulation rescues myotubular myopathy and prevents focal adhesion defects in mice

Centronuclear myopathies (CNMs) are severe diseases characterized by muscle weakness and myofiber atrophy. Currently, there are no approved treatments for these disorders. Mutations in the phosphoinositide 3-phosphatase myotubularin (MTM1) are responsible for X-linked CNM (XLCNM), also called myotubular myopathy, whereas mutations in the membrane remodeling Bin/amphiphysin/Rvs protein amphiphysin 2 [bridging integrator 1 (BIN1)] are responsible for an autosomal form of the disease. Here, we investigated the functional relationship between MTM1 and BIN1 in healthy skeletal muscle and in the physiopathology of CNM. Genetic overexpression of human BIN1 efficiently rescued the muscle weakness and life span in a mouse model of XLCNM. Exogenous human BIN1 expression with adeno-associated virus after birth also prevented the progression of the disease, suggesting that human BIN1 overexpression can compensate for the lack of MTM1 expression in this mouse model. Our results showed that MTM1 controls cell adhesion and integrin localization in mammalian muscle. Alterations in this pathway in Mtm1−/y mice were associated with defects in myofiber shape and size. BIN1 expression rescued integrin and laminin alterations and restored myofiber integrity, supporting the idea that MTM1 and BIN1 are functionally linked and necessary for focal adhesions in skeletal muscle. The results suggest that BIN1 modulation might be an effective strategy for treating XLCNM.

Mammalian skeletal muscle does not express functional voltage-gated H+ channels

High metabolic activity and existence of a large transmembrane inward electrochemical gradient for H+ at rest promote intracellular acidification of skeletal muscle. Exchangers and cotransports efficiently contend against accumulation of intracellular H+ and associated deleterious effects on muscle functions. Voltage-gated H+ channels have also been found to represent another H+ extrusion pathway in cultured muscle cells. Up to now, the skeletal muscle cell was therefore the unique vertebrate excitable cell in which voltage-gated H+ currents have been described. In this study, we show that, unlike cultured cells, single mouse muscle fibers do not generate H+ currents in response to depolarization. In contrast, expression of human voltage-gated H+ channels in mouse muscle gives rise to robust outward voltage-gated H+ currents. This result excludes that inappropriate experimental conditions may have failed to reveal voltage-gated H+ currents in control muscle. This work therefore demonstrates that fully differentiated mammalian muscle fibers do not express functional voltage-gated H+ channels and consequently can no longer be considered as the only vertebrate excitable cells exhibiting voltage-gated H+ currents.

On gonads and gadflies: the estrus angle

The first sex steroid to be crystallized was the vertebrate ovarian hormone, estrone – a less potent metabolite of 17β-estradiol, which in mammals stimulates the female urge to mate (estrus). The gadfly (Greek oistros) lent its name to the process of estrus, as an insect that bites and torments in classical Greek mythology. With the purification and crystallization of a moult-inducing steroid (ecdysone) from insects, an interesting parallel emerged between mating and moulting in lower mammals and arthropods. Ecdysterone (potent ecdysone metabolite) has anabolic effects in mammalian muscle cells that can be blocked by selective estrogen receptor antagonists. Insects utilize ecdysteroids in similar ways that vertebrates use estrogens, including stimulation of oocyte growth and maturation. Ecdysteroids also modify precopulatory insect mating behaviour, further reinforcing the gonad-gadfly/mate-moult analogy.