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Prelamin A causes aberrant myonuclear arrangement and results in muscle fiber weakness

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Yotam Levy, Jacob A. Ross, Marili Niglas, Vladimir A. Snetkov, Steven Lynham, Chen-Yu Liao, Megan Puckelwartz, Yueh-Mei Hsu, Elizabeth McNally, Manfred Alsheimer, Stephen D. R. Harridge, Stephen G. Young, Loren G. Fong, Yaiza Espanol, Carlos Lopez-Otin, Brian K. Kennedy, Dawn A. Lowe, Julien Ochala

Original languageEnglish
Article numbere120920
JournalJournal of Clinical Investigation Insight
Issue number19
Early online date4 Oct 2018
Accepted/In press24 Aug 2018
E-pub ahead of print4 Oct 2018
Published4 Oct 2018


King's Authors


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.

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