EB3 regulates microtubule dynamics at the cell cortex and is required for myoblast elongation and fusion

Anne Straube, Andreas Merdes

Research output: Contribution to journalArticlepeer-review

Abstract

During muscle differentiation, myoblasts elongate and fuse into syncytial myotubes [1]. An early event during this process is the remodeling of the microtubule cytoskeleton, involving disassembly of the centrosome and, crucially, the alignment of microtubules into a parallel array along the long axis of the cell [2-5]. To further our understanding on how microtubules support myogenic differentiation, we analyzed the role of EB1-related microtubule-plus-end-binding proteins. We demonstrate that EB3 [6] is specifically upregulated upon myogenic differentiation and that knockdown of EB3, but not that of EB1, prevents myoblast elongation and fusion into myotubes. EB3-depleted cells show disorganized microtubules and fail to stabilize polarized membrane protrusions. Using live-cell imaging, we show that EB3 is necessary for the regulation of microtubule dynamics and microtubule capture at the cell cortex. Expression of EB1/EB3 chimeras on an EB3-depletion background revealed that myoblast fusion depends on two specific amino acids in the calponin-like domain of EB3, whereas the interaction sites with Clip-170 and CLASPs are dispensable. Our results suggest that EB3-mediated microtubule regulation at the cell cortex is a crucial step during myogenic differentiation and might be a general mechanism in polarized cell elongation.
Original languageEnglish
Pages (from-to)1318-25
Number of pages8
JournalCurrent biology : CB
Volume17
Issue number15
DOIs
Publication statusPublished - 7 Aug 2007

Keywords

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Cell Differentiation
  • Cell Fusion
  • Cell Line
  • Cercopithecus aethiops
  • Extracellular Matrix
  • HeLa Cells
  • Humans
  • Mice
  • Microtubule-Associated Proteins
  • Microtubules
  • Molecular Sequence Data
  • Myoblasts
  • Protein Structure, Tertiary
  • Sequence Homology

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