Key result
In C. elegans, SRF does not depend on formin to promote muscle gene transcription, and formin contributes to muscle growth by an alternative mechanism involving proteolysis.
Why the study?
It was unclear whether endogenous formins promote SRF-dependent transcription during striated muscle development in vivo.
In C. elegans, SRF does not depend on formin to promote muscle gene transcription, suggesting formin contributes to muscle growth through alternative mechanisms such as regulating proteolysis.
No direct clinical implications; leaves open whether formin regulates muscle growth via proteolysis independently of SRF in mammals.
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 expression. However, while a hypomorphic unc-120 allele blunts transcription of a set of striated muscle genes, these genes are 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.
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Yingling et al. (2020) studied Striated muscle development. FHOD-1 absence and proteasome inhibition vs. Wild-type / uninhibited was evaluated on Muscle gene transcription and muscle growth. In C. elegans, SRF does not depend on formin to promote muscle gene transcription, and formin contributes to muscle growth by an alternative mechanism involving proteolysis.
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