A Nebulin Ruler Does Not Dictate Thin Filament Lengths

Angelica Castillo, Roberta Nowak, Kimberly P. Littlefield, Velia M. Fowler, Ryan S. Littlefield
2009 Biophysical Journal  
To generate force, striated muscle requires overlap between uniform-length actin and myosin filaments. The hypothesis that a nebulin ruler mechanism specifies thin filament lengths by targeting where tropomodulin (Tmod) caps the slow-growing, pointed end has not been rigorously tested. Using fluorescent microscopy and quantitative image analysis, we found that nebulin extended 1.01-1.03 mm from the Z-line, but Tmod localized 1.13-1.31 mm from the Z-line, in seven different rabbit skeletal
more » ... s. Because nebulin does not extend to the thin filament pointed ends, it can neither target Tmod capping nor specify thin filament lengths. We found instead a strong correspondence between thin filament lengths and titin isoform sizes for each muscle. Our results suggest the existence of a mechanism whereby nebulin specifies the minimum thin filament length and sarcomere length regulates and coordinates pointed-end dynamics to maintain the relative overlap of the thin and thick filaments during myofibril assembly.
doi:10.1016/j.bpj.2008.10.053 pmid:19254544 pmcid:PMC2717268 fatcat:oxa35fft3jfhlnbdv362zddfo4