Titin and Nebulin in Thick and Thin Filament Length Regulation

  • Larissa Tskhovrebova
  • John Trinick
Part of the Subcellular Biochemistry book series (SCBI, volume 82)


In this review we discuss the history and the current state of ideas related to the mechanism of size regulation of the thick (myosin) and thin (actin) filaments in vertebrate striated muscles. Various hypotheses have been considered during of more than half century of research, recently mostly involving titin and nebulin acting as templates or ‘molecular rulers’, terminating exact assembly. These two giant, single-polypeptide, filamentous proteins are bound in situ along the thick and thin filaments, respectively, with an almost perfect match in the respective lengths and structural periodicities. However, evidence still questions the possibility that the proteins function as templates, or scaffolds, on which the thin and thick filaments could be assembled. In addition, the progress in muscle research during the last decades highlighted a number of other factors that could potentially be involved in the mechanism of length regulation: molecular chaperones that may guide folding and assembly of actin and myosin; capping proteins that can influence the rates of assembly-disassembly of the myofilaments; Ca2+ transients that can activate or deactivate protein interactions, etc. The entire mechanism of sarcomere assembly appears complex and highly dynamic. This mechanism is also capable of producing filaments of about the correct size without titin and nebulin. What then is the role of these proteins? Evidence points to titin and nebulin stabilizing structures of the respective filaments. This stabilizing effect, based on linear proteins of a fixed size, implies that titin and nebulin are indeed molecular rulers of the filaments. Although the proteins may not function as templates in the assembly of the filaments, they measure and stabilize exactly the same size of the functionally important for the muscles segments in each of the respective filaments.


Vertebrate striated muscle Sarcomere structure Filaments lengths Molecular ruler hypothesis Titin/Connectin Nebulin 





Heat shock protein 90a


Intra-flagellar transport machinery


Myosin kinase inhibitor (and inhibitor to other kinases)


Myosin light chain kinase


Myosin binding protein-C (C-protein)


Ryanodine receptor




T-complex protein-1 ring complex


Protein unc-45 homolog B (unc45 myosin chaperone B)


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Astbury Centre, School of Molecular and Cellular Biology, Faculty of Biological SciencesUniversity of LeedsLeedsUK

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