
pmid: 15882626
The microtubule-organizing center (MTOC) is reoriented between the nucleus and the leading edge in many migrating cells and contributes to directional migration. Models suggest that the MTOC is moved to its position during reorientation. By direct imaging of wound-edge fibroblasts after triggering MTOC reorientation with soluble factors, we found instead that the nucleus moved away from the leading edge to reorient the MTOC, while the MTOC remained stationary. Rearward nuclear movement was coupled with actin retrograde flow and was regulated by a pathway involving Cdc42, MRCK, myosin, and actin. Nuclear movement was unaffected by the inhibition of dynein, Par6, or PKCzeta, yet these components were essential for MTOC reorientation, as they maintained the MTOC at the cell centroid. These results show that nuclear repositioning is an initial polarizing event in migrating cells and that the positions of the nucleus and the MTOC are established by separate regulatory pathways.
Cell Nucleus, Myosin Type II, Myosin Light Chains, Biochemistry, Genetics and Molecular Biology(all), Microfilament Proteins, Cell Polarity, Dyneins, Protein Serine-Threonine Kinases, Microtubules, Models, Biological, Actins, Culture Media, Serum-Free, Myotonin-Protein Kinase, Mice, Cell Movement, NIH 3T3 Cells, Animals, Phosphorylation, Carrier Proteins, Microtubule-Organizing Center, Protein Kinase C
Cell Nucleus, Myosin Type II, Myosin Light Chains, Biochemistry, Genetics and Molecular Biology(all), Microfilament Proteins, Cell Polarity, Dyneins, Protein Serine-Threonine Kinases, Microtubules, Models, Biological, Actins, Culture Media, Serum-Free, Myotonin-Protein Kinase, Mice, Cell Movement, NIH 3T3 Cells, Animals, Phosphorylation, Carrier Proteins, Microtubule-Organizing Center, Protein Kinase C
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