The sarcomeric protein nebulin: Another multifunctio giant in charge of muscle strength optimization

Coen A C Ottenheijm, Hendrikus "Henk" Granzier, Siegfried Labeit

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The sliding filament model of the sarcomere was developed more than half a century ago. This model, consisting only of thin and thick filaments, has been successful in explaining many, but not all, features of skeletal muscle. Work during the 1980s revealed the existence of two additional filaments: the giant filamentous proteins titin and nebulin. Whereas the role of titin rapidly progressed, nebulin's role in muscle structure and function remained long nebulous. An important feature of muscle structure and function that has remained relatively obscure concerns the mechanisms that are involved in regulating thin filament length. Filament length is an important aspect of muscle function as force production is proportional to the amount of overlap between thick and thin filaments. Recent advances, due in part to the generation of nebulin KO models, reveal that nebulin plays an important role in the regulation of thin filament length, most likely by stabilizing F-actin assemblies. Another structural feature of skeletal muscle that has been incompletely understood concerns the mechanisms involved in maintaining Z-disk structure and the regular lateral alignment of adjacent sarcomeres during contraction. Recent studies indicate that nebulin is part of a protein complex that mechanically links adjacent myofibrils. In addition to these structural roles in support of myofibrillar force generation, nebulin has been also shown to regulate directly muscle contraction at the level of individual crossbridges: cycling kinetics and the calcium sensitivity of force producing crossbridges is enhanced in the presence of nebulin. Thus, these recent data all point to nebulin being important for muscle force optimization. Consequently, muscle weakness as the lead symptom develops in the case of patients with nemaline myopathy that have mutations in the nebulin gene. Here, we discuss these important novel insights into the role of nebulin in skeletal muscle function.

Original languageEnglish (US)
Article numberArticle 37
JournalFrontiers in Physiology
Volume3 FEB
DOIs
StatePublished - 2012

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Muscle Strength
Proteins
Connectin
Muscles
Sarcomeres
Skeletal Muscle
Nemaline Myopathies
nebulin
Myofibrils
Muscle Weakness
Muscle Contraction
Actins
Calcium
Mutation

Keywords

  • Nebulin
  • Skeletal muscle
  • Thin filament

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

The sarcomeric protein nebulin : Another multifunctio giant in charge of muscle strength optimization. / Ottenheijm, Coen A C; Granzier, Hendrikus "Henk"; Labeit, Siegfried.

In: Frontiers in Physiology, Vol. 3 FEB, Article 37, 2012.

Research output: Contribution to journalArticle

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