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September 24, 2018Proceedings of the National Academy of SciencesOpen Access

Nebulin stiffens the thin filament and augments cross-bridge interaction in skeletal muscle

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Population

Intact skeletal muscle from conditional nebulin-knockout (Neb cKO) and control (Ctrl) models

Comparison

Nebulin deficiency (conditional nebulin-knockout) vs Control (Ctrl) muscle with intact nebulin

Design

Preclinical

Authors

BKBalázs KissSemmelweis UniversityELEun‐Jeong LeeLewis UniversityWMWeikang MaHeart Failure / Cardiomyopathy

Discussion

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Implication

Nebulin deficiency reduces thin filament stiffness and impairs cross-bridge recruitment; leaves open targeted therapies for nemaline myopathy.

Structured PICO

P
Population
Intact skeletal muscle from conditional nebulin-knockout (Neb cKO) and control (Ctrl) models
I
Intervention
Nebulin deficiency (conditional nebulin-knockout)
C
Comparator
Control (Ctrl) muscle with intact nebulin
O
Outcome
Thin filament stiffness, helical pitch, and cross-bridge interaction measured by small-angle X-ray diffractionsurrogate

Nebulin is critically important for physiological force levels by stiffening the skeletal muscle thin filament and contributing to activation and cross-bridge recruitment.

Cite This Study

Kiss et al. (2018) studied this question.

synapsesocial.com/papers/6a8ff9770691efebbb277d2chttps://doi.org/10.1073/pnas.1804726115
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Nebulin deficiency in adult muscle causes sarcomere defects and muscle-type-dependent changes in trophicity: novel insights in nemaline myopathy2015 · 69 citations
  2. 2Disrupted myosin cross‐bridge cycling kinetics triggers muscle weakness in nebulin‐related myopathy2011 · 64 citations
  3. 3Evidence that nebulin is a protein‐ruler in muscle thin filaments1991 · 205 citations
  4. 4A myopathy-linked tropomyosin mutation severely alters thin filament conformational changes during activation2010 · 52 citations
  5. 5Myopathy-inducing mutation H40Y in ACTA1 hampers actin filament structure and function2016 · 21 citations