Kif5b controls the localization of myofibril components for their assembly and linkage to the myotendinous junctions

Development. 2013 Feb 1;140(3):617-26. doi: 10.1242/dev.085969.

Abstract

Controlled delivery of myofibril components to the appropriate sites of assembly is crucial for myofibrillogenesis. Here, we show that kinesin-1 heavy chain Kif5b plays important roles in anterograde transport of α-sarcomeric actin, non-muscle myosin IIB, together with intermediate filament proteins desmin and nestin to the growing tips of the elongating myotubes. Mice with Kif5b conditionally knocked out in myogenic cells showed aggregation of actin filaments and intermediate filament proteins in the differentiating skeletal muscle cells, which further affected myofibril assembly and their linkage to the myotendinous junctions. The expression of Kif5b in mutant myotubes rescued the localization of the affected proteins. Functional mapping of Kif5b revealed a 64-amino acid α-helix domain in the tail region, which directly interacted with desmin and might be responsible for the transportation of these proteins in a complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Animals
  • Cell Differentiation
  • Desmin / genetics
  • Desmin / metabolism
  • Gene Expression Regulation, Developmental
  • Golgi Apparatus / metabolism
  • Golgi Apparatus / pathology
  • Green Fluorescent Proteins / metabolism
  • Hindlimb / metabolism
  • Hindlimb / pathology
  • Intercellular Junctions / metabolism*
  • Intermediate Filament Proteins / genetics
  • Intermediate Filament Proteins / metabolism
  • Kinesins / genetics
  • Kinesins / metabolism*
  • Mice
  • Mice, Knockout
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Muscle Development*
  • Muscle, Skeletal / metabolism
  • Muscular Dystrophy, Animal / metabolism
  • Muscular Dystrophy, Animal / pathology
  • Myoblasts, Skeletal / metabolism
  • Myoblasts, Skeletal / pathology
  • Myofibrils / genetics
  • Myofibrils / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nestin
  • Nonmuscle Myosin Type IIB / metabolism
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Structure, Tertiary
  • Protein Transport
  • Tendons / metabolism*

Substances

  • Desmin
  • Intermediate Filament Proteins
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Kif5b protein, mouse
  • Nonmuscle Myosin Type IIB
  • Kinesins