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 language | English |
---|---|
Pages (from-to) | 1318-25 |
Number of pages | 8 |
Journal | Current biology : CB |
Volume | 17 |
Issue number | 15 |
DOIs | |
Publication status | Published - 7 Aug 2007 |
Keywords / Materials (for Non-textual outputs)
- 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