Biology subjects

Pruyne, D.

Publications and source records attributed to Pruyne, D..

2 recordsLinked to original sources

bioRxiv2020

FHOD formin and SRF promote striated muscle development through separate pathways in C. elegans.

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 worms 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({Delta}) 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.

cell biology↗

bioRxiv2020

FHOD-1 is the only formin in Caenorhabditis elegans that promotes striated muscle growth and Z-line organization in a cell autonomous manner

The striated body wall muscles of Caenorhabditis elegans are a simple model system with well-characterized sarcomeres that have many vertebrate protein homologs. Previously, we observed deletion mutants for two formin genes, fhod-1 and cyk-1, developed thin muscles with abnormal dense bodies/sarcomere Z-lines. However, the nature of the cyk-1 mutation necessitated maternal CYK-1 expression for viability of the examined animals. Here, we tested the effects of complete loss of CYK-1 using a fast acting temperature-sensitive cyk-1(ts) mutant. Surprisingly, neither post-embryonic loss of CYK-1 nor acute loss of CYK-1 during embryonic sarcomerogenesis caused muscle defects, suggesting CYK-1 might not play a direct role in muscle development. Consistent with this, examination of cyk-1({Delta}) mutants re-expressing CYK-1 in a mosaic pattern showed CYK-1 cannot rescue muscle defects in a muscle cell autonomous manner, suggesting muscle phenotypes caused by cyk-1 deletion are likely indirect. Conversely, mosaic re-expression of FHOD-1 in fhod-1({Delta}) mutants promoted muscle cell growth, as well as proper Z-line organization, in a muscle cell autonomous manner. As we can observe no effect of loss of any other worm formin on muscle development, we conclude that FHOD-1 is the only formin that directly promotes striated muscle development in C. elegans.

developmental biology↗