Par6alpha Signaling Controls Glial-Guided Neuronal Migration

Nat Neurosci. 2004 Nov;7(11):1195-203. doi: 10.1038/nn1332. Epub 2004 Oct 10.

Abstract

Neuronal migrations along glial fibers provide a primary pathway for the formation of cortical laminae. To examine the mechanisms underlying glial-guided migration, we analyzed the dynamics of cytoskeletal and signaling components in living neurons. Migration involves the coordinated two-stroke movement of a perinuclear tubulin 'cage' and the centrosome, with the centrosome moving forward before nuclear translocation. Overexpression of mPar6alpha disrupts the perinuclear tubulin cage, retargets PKCzeta and gamma-tubulin away from the centrosome, and inhibits centrosomal motion and neuronal migration. Thus, we propose that during neuronal migration the centrosome acts to coordinate cytoskeletal dynamics in response to mPar6alpha-mediated signaling.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / physiology*
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Cell Nucleus / metabolism
  • Cell Polarity / physiology
  • Cell Surface Extensions / drug effects
  • Cell Surface Extensions / physiology
  • Cells, Cultured
  • Centrosome / metabolism
  • Cerebellum / cytology*
  • Cloning, Molecular / methods
  • Coculture Techniques / methods
  • Diagnostic Imaging / methods
  • Dynactin Complex
  • Genetic Vectors / physiology
  • Glial Fibrillary Acidic Protein / metabolism
  • Green Fluorescent Proteins / metabolism
  • Immunohistochemistry / methods
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurons / virology
  • Organ Culture Techniques
  • Photobleaching
  • Protein Kinase C / metabolism
  • Protein Kinase C-epsilon
  • Proteins / genetics
  • Proteins / metabolism
  • Proteins / physiology*
  • RNA, Catalytic / pharmacology
  • Signal Transduction / physiology*
  • Time Factors
  • Transfection / methods
  • Tubulin / metabolism
  • Videotape Recording / methods
  • Zidovudine / metabolism

Substances

  • Dynactin Complex
  • Glial Fibrillary Acidic Protein
  • Microtubule-Associated Proteins
  • Proteins
  • RNA, Catalytic
  • Tubulin
  • hairpin ribozyme
  • Green Fluorescent Proteins
  • Zidovudine
  • Prkce protein, mouse
  • Protein Kinase C
  • Protein Kinase C-epsilon