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

Edgar R Gomes1, Shantanu Jani, Gregg G Gundersen

  • 1Department of Anatomy and Cell Biology, Columbia University, New York, NY 10032, USA.

Cell
|May 11, 2005
PubMed

Insights

Cell migration involves microtubule-organizing center (MTOC) reorientation. This study reveals that the nucleus moves away from the cell edge, repositioning the MTOC and guiding cell migration.

Area of Science:

  • Cell Biology
  • Cytoskeleton Dynamics
  • Cell Migration

Background:

  • Microtubule-organizing center (MTOC) reorientation is crucial for directional cell migration.
  • Previous models proposed MTOC movement during reorientation.

Purpose of the Study:

  • To investigate the mechanism of MTOC reorientation in migrating fibroblasts.
  • To determine the roles of nuclear positioning and cytoskeletal components in MTOC reorientation.

Main Methods:

  • Direct live-cell imaging of wound-edge fibroblasts.
  • Stimulation of MTOC reorientation using soluble factors.
  • Perturbation of specific molecular pathways (Cdc42, myosin, actin, dynein, Par6, PKCzeta).

Main Results:

  • The nucleus moves away from the leading edge, while the MTOC remains stationary during reorientation.
  • Rearward nuclear movement is linked to actin retrograde flow and regulated by Cdc42, MRCK, myosin, and actin.
  • Dynein, Par6, and PKCzeta are not required for nuclear movement but are essential for maintaining MTOC position at the cell centroid.

Conclusions:

  • Nuclear repositioning precedes and facilitates MTOC reorientation in migrating cells.
  • Nuclear and MTOC positioning are regulated by distinct molecular pathways.
  • This study redefines the initial events in cell polarization during migration.

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