Prelamin A causes aberrant myonuclear arrangement and results in muscle fiber weakness
| Autor: | Levy, Yotam, Ross, Jacob A., Niglas, Marili, Snetkov, Vladimir A., Lynham, Steven, Liao, Chen-Yu, Puckelwartz, Megan J., Hsu, Yueh-Mei, McNally, Elizabeth M., Alsheimer, Manfred, Harridge, Stephen D.R., Young, Stephen G., Fong, Loren G., Español, Yaiza, Lopez-Otin, Carlos, Kennedy, Brian K., Lowe, Dawn A., Ochala, Julien |
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| Rok vydání: | 2018 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Aging Cell Membrane Permeability Cells Knockout Muscle Fibers Skeletal Primary Cell Culture Myosins Muscle Fibers Mice Genetics Animals Humans 2.1 Biological and endogenous factors Muscle Strength Premature Cells Cultured Mice Knockout Cell Nucleus Cultured integumentary system Animal Cell Membrane Aging Premature Skeletal Neuromuscular disease Lamin Type A Disease Models Animal Disease Models Muscle Biology Research Article Genetic diseases |
| Zdroj: | JCI insight, vol 3, iss 19 Levy, Y, Ross, J A, Niglas, M, Snetkov, V, Lynham, S, Liao, C-Y, Puckelwartz, M, Hsu, Y-M, McNally, E, Alsheimer, M, Harridge, S D R, Young, S G, Fong, L G, Espanol, Y, Lopez-Otin, C, Kennedy, B K, Lowe, D A & Ochala, J 2018, ' Prelamin A causes aberrant myonuclear arrangement and results in muscle fiber weakness ', JCI Insight, vol. 3, no. 19, e120920 . https://doi.org/10.1172/jci.insight.120920 JCI Insight |
| Popis: | Physiological and premature aging are frequently associated with an accumulation of prelamin A, a precursor of lamin A, in the nuclear envelope of various cell types. Here, we aimed to underpin the hitherto unknown mechanisms by which prelamin A alters myonuclear organization and muscle fiber function. By experimentally studying membrane-permeabilized myofibers from various transgenic mouse lines, our results indicate that, in the presence of prelamin A, the abundance of nuclei and myosin content is markedly reduced within muscle fibers. This leads to a concept by which the remaining myonuclei are very distant from each other and are pushed to function beyond their maximum cytoplasmic capacity, ultimately inducing muscle fiber weakness. Following prelamin A accumulation in myofibers, the abundance of nuclei and myosin content within muscle fibers is reduced, ultimately inducing muscle fiber weakness. |
| Databáze: | OpenAIRE |
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