Reference - Detail
| RRC ID | 84069 |
|---|---|
| Author | Kimmich MJ, Sundaramurthy S, Geary MA, Lesanpezeshki L, Yingling CV, Vanapalli SA, Littlefield RS, Pruyne D. |
| Title | FHOD-1 and profilin protect sarcomeres against contraction-induced deformation> in C. elegans. |
| Journal | Mol Biol Cell |
| Abstract |
Formin HOmology Domain 2-containing (FHOD) proteins are a subfamily of actin-organizing formins important for striated muscle development in many animals. We showed previously that absence of the sole FHOD protein, FHOD-1, from Caenorhabditis elegans results in thin body wall muscles with misshapen dense bodies that serve as sarcomere Z-lines. We demonstrate here that mutations predicted to specifically disrupt actin polymerization by FHOD-1 similarly disrupt muscle development, and that FHOD-1 cooperates with profilin PFN-3 for dense body morphogenesis, and with profilins PFN-2 and PFN-3 to promote body wall muscle growth. We further demonstrate that dense bodies in worms lacking FHOD-1 or PFN-2/PFN-3 are less stable than in wild-type animals, having a higher proportion of dynamic protein, and becoming distorted by prolonged muscle contraction. We also observe accumulation of actin and actin depolymerization factor/cofilin homologue UNC-60B in body wall muscle of these mutants. Such accumulations may indicate targeted disassembly of thin filaments dislodged from unstable dense bodies, possibly accounting for the abnormally slow growth and reduced body wall muscle strength in fhod-1 mutants. Overall, these results implicate FHOD protein-mediated actin assembly in forming stable sarcomere Z-lines, and identify profilin as a new contributor to FHOD activity in striated muscle development. |
| Volume | 35(11) |
| Pages | ar137 |
| Published | 2024-11-1 |
| DOI | 10.1091/mbc.E24-04-0145 |
| PMID | 39259762 |
| PMC | PMC11617102 |
| MeSH | Actin Cytoskeleton / metabolism Actin Depolymerizing Factors / metabolism Actins* / metabolism Animals Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Formins* / metabolism Microfilament Proteins / genetics Microfilament Proteins / metabolism Muscle Contraction* / physiology Muscle Development / physiology Muscle, Striated / metabolism Muscles / metabolism Mutation / genetics Profilins* / genetics Profilins* / metabolism Sarcomeres* / metabolism |
| Altmetric score |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 5 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm1362 tm2363 |