Nuclear actin and Mrtfs control disuse muscle atrophy via Srf activity regulation
| Autor: | Aline Guerci, Voahangy Randrianarison-Huetz, Gaëlle Herledan, Laura Collard, Alessandra Pincini, Athanassia Sotiropoulos |
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| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
genetic structures Skeletal muscle Cell Biology Biology musculoskeletal system medicine.disease eye diseases Muscle atrophy Cell biology medicine.anatomical_structure Endocrinology Atrophy Myocardin Internal medicine embryonic structures Serum response factor cardiovascular system medicine Mechanotransduction medicine.symptom Transcription factor Actin |
| Zdroj: | Journal of Cell Science. |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | Skeletal muscle atrophy is a debilitating process that is associated with a wide variety of conditions including inactivity, disease and aging. Here, we demonstrate that the actin, myocardin-related transcription factors and serum response factor (actin-Mrtf-Srf) pathway is specifically downregulated in the muscle atrophy that is induced through disuse in mice. We show in vivo that the abolition of mechanical signals leads to the rapid accumulation of G-actin in myonuclei and the export of the Srf coactivator Mrtf-A, resulting in a decrease of Mrtf-Srf-dependent transcription that contributes to atrophy. We demonstrate that inhibition of the actin-Mrtf-Srf axis through overexpression of nuclear non-polymerizable actin, through pharmacological inhibition of Mrtf-Srf and through muscle-specific Srf deletion worsens denervation-induced atrophy. Conversely, maintenance of high levels of activity of Srf or Mrtfs in denervated muscle, through overexpression of constitutively active derivatives, counteracts atrophy. Altogether, our data provide new mechanistic insights into the control of muscle mass upon disuse atrophy by the actin-Mrtf-Srf pathway, highlighting Srf as a key mediator of mechanotransduction in muscle. |
| Databáze: | OpenAIRE |
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