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The N-terminal end of nebulin interacts with tropomodulin at the pointed ends of the thin filaments

Academic Article
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Overview

authors

  • McElhinny, A. S.
  • Kolmerer, B.
  • Fowler, Velia
  • Labeit, S.
  • Gregorio, C. C.

publication date

  • January 2001

journal

  • Journal of Biological Chemistry  Journal

abstract

  • Strict regulation of actin thin filament length is critical for the proper functioning of sarcomeres, the basic contractile units of myofibrils. It has been hypothesized that a molecular template works with actin filament capping proteins to regulate thin filament lengths. Nebulin is a giant protein ( approximately 800 kDa) in skeletal muscle that has been proposed to act as a molecular ruler to specify the thin filament lengths characteristic of different muscles. Tropomodulin (Tmod), a pointed end thin filament capping protein, has been shown to maintain the final length of the thin filaments. Immunofluorescence microscopy revealed that the N-terminal end of nebulin colocalizes with Tmod at the pointed ends of thin filaments. The three extreme N-terminal modules (M1-M2-M3) of nebulin bind specifically to Tmod as demonstrated by blot overlay, bead binding, and solid phase binding assays. These data demonstrate that the N terminus of the nebulin molecule extends to the extreme end of the thin filament and also establish a novel biochemical function for this end. Two Tmod isoforms, erythrocyte Tmod (E-Tmod), expressed in embryonic and slow skeletal muscle, and skeletal Tmod (Sk-Tmod), expressed late in fast skeletal muscle differentiation, bind on overlapping sites to recombinant N-terminal nebulin fragments. Sk-Tmod binds nebulin with higher affinity than E-Tmod does, suggesting that the Tmod/nebulin interaction exhibits isoform specificity. These data provide evidence that Tmod and nebulin may work together as a linked mechanism to control thin filament lengths in skeletal muscle.

subject areas

  • Actin Cytoskeleton
  • Actins
  • Animals
  • Binding Sites
  • Biotinylation
  • Carrier Proteins
  • Fluorescent Antibody Technique
  • Humans
  • Microfilament Proteins
  • Models, Molecular
  • Molecular Sequence Data
  • Muscle Proteins
  • Muscle, Skeletal
  • Peptide Fragments
  • Protein Binding
  • Protein Structure, Tertiary
  • Rats
  • Recombinant Proteins
  • Solutions
  • Substrate Specificity
  • Tropomodulin
  • Tropomyosin
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Identity

International Standard Serial Number (ISSN)

  • 0021-9258

PubMed ID

  • 11016930
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Additional Document Info

start page

  • 583

end page

  • 592

volume

  • 276

issue

  • 1

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