FHOD formin and SRF promote post-embryonic striated muscle growth through separate pathways in C. elegans

Exp Cell Res. 2021 Jan 1;398(1):112388. doi: 10.1016/j.yexcr.2020.112388. Epub 2020 Nov 20.


Previous work with cultured cells has shown transcription of muscle genes by serum response factor (SRF) can be stimulated by actin polymerization driven by proteins of the formin family. However, it is not clear if endogenous formins similarly promote SRF-dependent transcription during muscle development in vivo. We tested whether formin activity promotes SRF-dependent transcription in striated muscle in the simple animal model, Caenorhabditis elegans. Our lab has shown FHOD-1 is the only formin that directly promotes sarcomere formation in the worm's striated muscle. We show here FHOD-1 and SRF homolog UNC-120 both support muscle growth and also muscle myosin II heavy chain A expression. However, while a hypomorphic unc-120 allele blunts expression of a set of striated muscle genes, these genes are largely upregulated or unchanged by absence of FHOD-1. Instead, pharmacological inhibition of the proteasome restores myosin protein levels in worms lacking FHOD-1, suggesting elevated proteolysis accounts for their myosin deficit. Interestingly, proteasome inhibition does not restore normal muscle growth to fhod-1(Δ) mutants, suggesting formin contributes to muscle growth by some alternative mechanism. Overall, we find SRF does not depend on formin to promote muscle gene transcription in a simple in vivo system.

Keywords: Caenorhabditis elegans; FHOD-1; Formin; Proteasome; Serum response factor; Striated muscle.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Proliferation
  • Formins / genetics
  • Formins / metabolism*
  • Muscle, Striated / metabolism*
  • Serum Response Factor / genetics
  • Serum Response Factor / metabolism*


  • Caenorhabditis elegans Proteins
  • Formins
  • Serum Response Factor
  • fhod-1 proteins, C elegans