Microtubule-induced Pins/Galphai cortical polarity in Drosophila neuroblasts

Cell. 2005 Dec 29;123(7):1323-35. doi: 10.1016/j.cell.2005.09.043.

Abstract

Cortical polarity regulates cell division, migration, and differentiation. Microtubules induce cortical polarity in yeast, but few examples are known in metazoans. We show that astral microtubules, kinesin Khc-73, and Discs large (Dlg) induce cortical polarization of Pins/Galphai in Drosophila neuroblasts; this cortical domain is functional for generating spindle asymmetry, daughter-cell-size asymmetry, and distinct sibling fates. Khc-73 localizes to astral microtubule plus ends, and Dlg/Khc-73 and Dlg/Pins coimmunoprecipitate, suggesting that microtubules induce Pins/Galphai cortical polarity through Dlg/Khc-73 interactions. The microtubule/Khc-73/Dlg pathway acts in parallel to the well-characterized Inscuteable/Par pathway, but each provides unique spatial and temporal information: The Inscuteable/Par pathway initiates at prophase to coordinate neuroblast cortical polarity with CNS tissue polarity, whereas the microtubule/Khc-73/Dlg pathway functions at metaphase to coordinate neuroblast cortical polarity with the mitotic spindle axis. These results identify a role for microtubules in polarizing the neuroblast cortex, a fundamental step for generating cell diversity through asymmetric cell division.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Cycle Proteins
  • Cell Polarity / physiology*
  • Cells, Cultured
  • Drosophila
  • Drosophila Proteins / metabolism*
  • Drosophila Proteins / physiology
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism*
  • Guanine Nucleotide Dissociation Inhibitors / metabolism*
  • Kinesin / physiology
  • Metaphase
  • Microtubules / physiology*
  • Models, Biological
  • Nerve Tissue Proteins / physiology
  • Neurons / cytology
  • Neurons / metabolism*
  • Spindle Apparatus / physiology
  • Tumor Suppressor Proteins / physiology

Substances

  • Cell Cycle Proteins
  • Drosophila Proteins
  • Guanine Nucleotide Dissociation Inhibitors
  • Khc-73 protein, Drosophila
  • Nerve Tissue Proteins
  • Pins protein, Drosophila
  • Tumor Suppressor Proteins
  • dlg1 protein, Drosophila
  • Kinesin
  • GTP-Binding Protein alpha Subunits, Gi-Go