Drosophila Tropomodulin is required for multiple actin-dependent processes within developing myofibers

Development. 2023 Mar 15;150(6):dev201194. doi: 10.1242/dev.201194. Epub 2023 Mar 24.

Abstract

Proper muscle contraction requires the assembly and maintenance of sarcomeres and myofibrils. Although the protein components of myofibrils are generally known, less is known about the mechanisms by which they individually function and together synergize for myofibril assembly and maintenance. For example, it is unclear how the disruption of actin filament (F-actin) regulatory proteins leads to the muscle weakness observed in myopathies. Here, we show that knockdown of Drosophila Tropomodulin (Tmod), results in several myopathy-related phenotypes, including reduction of muscle cell (myofiber) size, increased sarcomere length, disorganization and misorientation of myofibrils, ectopic F-actin accumulation, loss of tension-mediating proteins at the myotendinous junction, and misshaped and internalized nuclei. Our findings support and extend the tension-driven self-organizing myofibrillogenesis model. We show that, like its mammalian counterpart, Drosophila Tmod caps F-actin pointed-ends, and we propose that this activity is crucial for cellular processes in different locations within the myofiber that directly and indirectly contribute to the maintenance of muscle function. Our findings provide significant insights to the role of Tmod in muscle development, maintenance and disease.

Keywords: Drosophila; Misshapen nuclei; Myofibril orientation; Sarcomere length; Skeletal muscle; Tension-mediating proteins; Tropomodulin (Tmod).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins* / metabolism
  • Animals
  • Drosophila / genetics
  • Drosophila / metabolism
  • Mammals / metabolism
  • Microfilament Proteins / metabolism
  • Myofibrils / metabolism
  • Sarcomeres / metabolism
  • Tropomodulin* / genetics
  • Tropomodulin* / metabolism

Substances

  • Actins
  • Tropomodulin
  • Microfilament Proteins