4.8 Article

Septin7 is indispensable for proper skeletal muscle architecture and function

Journal

ELIFE
Volume 11, Issue -, Pages -

Publisher

eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.75863

Keywords

septins; cytoskeleton; skeletal muscle; mitochondria; development; regeneration; Human; Mouse

Categories

Funding

  1. National Research, Development and Innovation Fund of Hungary [NKFIH K-137600, TKP2020-NKA-04]
  2. Hungarian National Research, Development and Innovation Office [2020-4.1.1-TKP2020]
  3. European Union [NKFIH K-137600, GINOP-2.3.2-15-2016-00044]
  4. [GINOP-2.3.3-15-2016-00020]

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This study reveals the important role of Septin7 in skeletal muscle, specifically in muscle regeneration and development. Knockout of Septin7 leads to hunchback phenotype, skeletal deformities, reduction in force generation, and disorganized mitochondrial networks.
Today septins are considered as the fourth component of the cytoskeleton, with the Septin7 isoform playing a critical role in the formation of higher-order structures. While its importance has already been confirmed in several intracellular processes of different organs, very little is known about its role in skeletal muscle. Here, using Septin7 conditional knockdown (KD) mouse model, the C2C12 cell line, and enzymatically isolated adult muscle fibers, the organization and localization of septin filaments are revealed, and an ontogenesis-dependent expression of Septin7 is demonstrated. KD mice displayed a characteristic hunchback phenotype with skeletal deformities, reduction in in vivo and in vitro force generation, and disorganized mitochondrial networks. Furthermore, knockout of Septin7 in C2C12 cells resulted in complete loss of cell division while KD cells provided evidence that Septin7 is essential for proper myotube differentiation. These and the transient increase in Septin7 expression following muscle injury suggest that it may be involved in muscle regeneration and development.

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