Abstract
Lamination of cortical regions of the vertebrate brain depends on glial-guided neuronal migration. The conserved polarity protein Par6alpha localizes to the centrosome and coordinates forward movement of the centrosome and soma in migrating neurons. The cytoskeletal components that produce this unique form of cell polarity and their relationship to polarity signaling cascades are unknown. We show that F-actin and Myosin II motors are enriched in the neuronal leading process and that Myosin II activity is necessary for leading process actin dynamics. Inhibition of Myosin II decreased the speed of centrosome and somal movement, whereas Myosin II activation increased coordinated movement. Ectopic expression or silencing of Par6alpha inhibited Myosin II motors by decreasing Myosin light-chain phosphorylation. These findings suggest leading-process Myosin II may function to "pull" the centrosome and soma forward during glial-guided migration by a mechanism involving the conserved polarity protein Par6alpha.
| Original language | English |
|---|---|
| Pages (from-to) | 63-80 |
| Number of pages | 18 |
| Journal | Neuron |
| Volume | 63 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jul 16 2009 |
| Externally published | Yes |
Funding
We are grateful to Drs. Linda Van Aelst and Bob Adelstein for critically reading the manuscript, Dr. Rick Horwitz for helpful discussions, and Dr. Jakub Famulski for aiding with the shRNA experiments. We are indebted to Dr. Bill Bement for providing the panel of UTRCH-ABD vectors and Dr. Atsushi Miyawaki for providing the Venus reporter. We also thank Dr. Anne Bresnick for the MLCK cDNA, Dr. Shuh Narumiya for the Rock1 cDNA, Dr. Gary Banker for the Map2C cDNA, Dr. Ken Jacobson for the Paxillin cDNA, and Greg Law (Perkin Elmer) for the extended use of an Ultraview confocal microscope. We also thank Dr. Regan Baird and Intelligent Imaging Innovations for setting up our Marianas Workstation and developing Slidebook tools for volumetric and line-scanning analysis. This work was supported by American Lebanese Syrian Associated Charities (ALSAC; D.J.S.), NCI 2 P30CA021765-30 (D.J.S.), a March of Dimes Basil O'Connor Starter Scholar Research Award (D.J.S.), and NIH grants R01-NS15429-26 (M.E.H.) and R01 NS051778-02 (M.E.H.).