Nebulin, a major player in muscle health and disease

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

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Nebulin is a giant 600-to 900-kDa filamentous protein that is an integral component of the skeletal muscle thin filament. Its functions have remained largely nebulous because of its large size and the difficulty in extracting nebulin in a native state from muscle. Recent improvements in the field, especially the development of knockout mouse models deficient in nebulin (NEB-KO mice), indicate now that nebulin performs a surprisingly wide range of functions. In addition to a major role in thin-filament length specification, nebulin also functions in the regulation of muscle contraction, as indicated by the findings that muscle fibers deficient in nebulin have a higher tension cost, and develop less force due to reduced myofilament calcium sensitivity and altered crossbridge cycling kinetics. In addition, the function of nebulin extends to a role in calcium homeostasis. These novel functions indicate that nebulin might have evolved in vertebrate skeletal muscles to develop high levels of muscle force efficiently. Finally, the NEB-KO mouse models also highlight the role of nebulin in the assembly and alignment of the Z disks. Notably, rapid progress in understanding the roles of nebulin in vivo provides clinically important insights into how nebulin deficiency in patients with nemaline myopathy contributes to debilitating muscle weakness.

Original languageEnglish (US)
Pages (from-to)822-829
Number of pages8
JournalFASEB Journal
Volume25
Issue number3
DOIs
StatePublished - Mar 2011

Fingerprint

Muscle
Health
Muscles
Skeletal Muscle
nebulin
Nemaline Myopathies
Calcium
Myofibrils
Muscle Weakness
Muscle Contraction
Knockout Mice
Vertebrates
Homeostasis
Specifications
Costs and Cost Analysis
Kinetics
Fibers

Keywords

  • Calcium sensitivity
  • Muscle contraction
  • Nemaline myopathy
  • Regulation
  • Sarcolipin

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Nebulin, a major player in muscle health and disease. / Labeit, Siegfried; Ottenheijm, Coen A C; Granzier, Hendrikus "Henk".

In: FASEB Journal, Vol. 25, No. 3, 03.2011, p. 822-829.

Research output: Contribution to journalArticle

Labeit, Siegfried ; Ottenheijm, Coen A C ; Granzier, Hendrikus "Henk". / Nebulin, a major player in muscle health and disease. In: FASEB Journal. 2011 ; Vol. 25, No. 3. pp. 822-829.
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