A nebulin ruler does not dictate thin filament lengths

Biophys J. 2009 Mar 4;96(5):1856-65. doi: 10.1016/j.bpj.2008.10.053.


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 mum from the Z-line, but Tmod localized 1.13-1.31 mum from the Z-line, in seven different rabbit skeletal muscles. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Chickens
  • Female
  • Fluorescent Antibody Technique
  • Male
  • Muscle Proteins / chemistry
  • Muscle Proteins / metabolism*
  • Muscle, Striated / metabolism*
  • Muscle, Striated / ultrastructure
  • Myofibrils / metabolism*
  • Myofibrils / ultrastructure
  • Rabbits
  • Tropomodulin / chemistry
  • Tropomodulin / metabolism


  • Actins
  • Muscle Proteins
  • Tropomodulin
  • nebulin