RESUMEN
Here, we investigated the mechanisms by which aging-related reductions of the levels of Numb in skeletal muscle fibers contribute to loss of muscle strength and power, two critical features of sarcopenia. Numb is an adaptor protein best known for its critical roles in development, including asymmetric cell division, cell-type specification, and termination of intracellular signaling. Numb expression is reduced in old humans and mice. We previously showed that, in mouse skeletal muscle fibers, Numb is localized to sarcomeres where it is concentrated near triads; conditional inactivation of Numb and a closely related protein Numb-like (Numbl) in mouse myofibers caused weakness, disorganization of sarcomeres, and smaller mitochondria with impaired function. Here, we found that a single knockout of Numb in myofibers causes reduction in tetanic force comparable to a double Numb, Numbl knockout. We found by proteomics analysis of protein complexes isolated from C2C12 myotubes by immunoprecipitation using antibodies against Numb that Septin 7 is a potential Numb-binding partner. Septin 7 is a member of the family of GTP-binding proteins that organize into filaments, sheets, and rings, and is considered part of the cytoskeleton. Immunofluorescence evaluation revealed a partial overlap of staining for Numb and Septin 7 in myofibers. Conditional, inducible knockouts of Numb led to disorganization of Septin 7 staining in myofibers. These findings indicate that Septin 7 is a Numb-binding partner and suggest that interactions between Numb and Septin 7 are critical for structural organization of the sarcomere and muscle contractile function.
Asunto(s)
Péptidos y Proteínas de Señalización Intracelular , Proteínas de la Membrana , Ratones Noqueados , Contracción Muscular , Proteínas del Tejido Nervioso , Sarcómeros , Septinas , Animales , Septinas/metabolismo , Septinas/genética , Sarcómeros/metabolismo , Ratones , Contracción Muscular/fisiología , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Unión Proteica , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/fisiologíaRESUMEN
Physical activity is an especially important part of everyday life for children with chronic diseases. The aim of the study was to show whether asthma is a barrier to physical activity in our society. The correlations between the severity of the disease, body mass index, and physical activity were analyzed, and parents' opinions on whether children should participate in active sports were assessed. Physical activity of children with asthma was analyzed by questionnaires; 93 parents and their 93 children were involved in the survey. The age of children was 12.6 ± 3.5 years (mean ± SD), 69.9% were boys, 30.1% were girls. A total of 93.4% of the respondents participated in a physical education program and 56.5% also attended sporting activities on a regular basis. In terms of disease severity, 61.2% of the children had mild asthma, 37.6% moderate, and 1.2% severe, and 6.5% of the respondents also stated that their children's illness had been consistently or frequently limiting their performance concerning their school or home duties over the past four weeks. Of the parents surveyed, 12% felt that physical activity was not appropriate in the context of this disease. We concluded that fear of the consequences of physical activity depends largely on education, which should involve parents, teachers, and coaches.