Discs large 5 is required for polarization of citron kinase in mitotic neural precursors

Cell Cycle. 2010 May 15;9(10):1990-7. doi: 10.4161/cc.9.10.11730. Epub 2010 May 15.

Abstract

Citron kinase (CitK), a protein essential to neurogenic cell division in the central nervous system, is highly polarized in neural progenitors. The mechanisms that polarize CitK to cellular domains that line the ventricular surface of neuroepithelium are currently not known. Here we report that Discs large 5 (Dlg5), a member of the MAGUK family, is an interactor of CitK required for CitK polarization. The CitK-Dlg5 interaction was first revealed in a protein array screen of proteins containing PDZ domains, and then subsequently confirmed by co-immunoprecipitation. Moreover, in Dlg5 (-/-) mice CitK fails to polarize in mitotic neuronal precursors. In addition, the total number of mitotic progenitors and the ratio of ventricular to abventricular mitotic progenitors in developing neocortex are significantly decreased in Dlg5 (-/-) embryos. Dlg5 is therefore required to maintain the polarization of a protein essential to neurogenic cytokinesis, and plays a role in localizing cell divisions to the surface of the lateral ventricles in embryonic brain.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain / embryology
  • Brain / metabolism
  • Cell Division / physiology
  • Cells, Cultured
  • Guanylate Kinases / genetics
  • Guanylate Kinases / metabolism*
  • Immunohistochemistry
  • Immunoprecipitation
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lateral Ventricles / embryology
  • Lateral Ventricles / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Mitosis / genetics
  • Mitosis / physiology
  • Neurons / cytology*
  • Neurons / metabolism*
  • Protein Binding
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Rats

Substances

  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • citron-kinase
  • Protein-Serine-Threonine Kinases
  • Dlg5 protein, mouse
  • Guanylate Kinases