Nuclear movement regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells

被引:466
作者
Gomes, ER
Jani, S
Gundersen, GG [1 ]
机构
[1] Columbia Univ, Dept Anat & Cell Biol, New York, NY 10032 USA
[2] Columbia Univ, Dept Pathol, New York, NY 10032 USA
关键词
D O I
10.1016/j.cell.2005.02.022
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 PKC zeta, 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.
引用
收藏
页码:451 / 463
页数:13
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