A novel isoform of MAP4 organises the paraxial microtubule array required for muscle cell differentiation

Elife. 2015 Apr 21;4:e05697. doi: 10.7554/eLife.05697.

Abstract

The microtubule cytoskeleton is critical for muscle cell differentiation and undergoes reorganisation into an array of paraxial microtubules, which serves as template for contractile sarcomere formation. In this study, we identify a previously uncharacterised isoform of microtubule-associated protein MAP4, oMAP4, as a microtubule organising factor that is crucial for myogenesis. We show that oMAP4 is expressed upon muscle cell differentiation and is the only MAP4 isoform essential for normal progression of the myogenic differentiation programme. Depletion of oMAP4 impairs cell elongation and cell-cell fusion. Most notably, oMAP4 is required for paraxial microtubule organisation in muscle cells and prevents dynein- and kinesin-driven microtubule-microtubule sliding. Purified oMAP4 aligns dynamic microtubules into antiparallel bundles that withstand motor forces in vitro. We propose a model in which the cooperation of dynein-mediated microtubule transport and oMAP4-mediated zippering of microtubules drives formation of a paraxial microtubule array that provides critical support for the polarisation and elongation of myotubes.

Keywords: cell biology; microtubule organisation; microtubule-associated proteins; molecular motors; mouse; none.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line
  • Cell Movement
  • Cloning, Molecular
  • Cytoskeleton / metabolism
  • Cytoskeleton / ultrastructure
  • Dyneins / genetics
  • Dyneins / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Kinesin / genetics
  • Kinesin / metabolism
  • Mice
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / metabolism*
  • Microtubules / ultrastructure
  • Muscle Development / genetics*
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / metabolism*
  • Myoblasts, Skeletal / cytology
  • Myoblasts, Skeletal / metabolism*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sarcomeres / metabolism
  • Sarcomeres / ultrastructure

Substances

  • MAP4
  • Microtubule-Associated Proteins
  • Protein Isoforms
  • Recombinant Proteins
  • Dyneins
  • Kinesin