Microtubule-induced Pins/Galphai cortical polarity in Drosophila neuroblasts.
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.
Siegrist
Sarah E
SE
Institutes of Neuroscience and Molecular Biology, Howard Hughes Medical Institute, University of Oregon, Eugene, Oregon 97403, USA.
Doe
Chris Q
CQ
D000818:Animals; D030801:Animals, Genetically Modified; D018797:Cell Cycle Proteins; D016764:Cell Polarity / Q000502:physiology*; D002478:Cells, Cultured; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism* / Q000502:physiology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism*; D016547:Kinesins / Q000502:physiology; D008677:Metaphase; D008870:Microtubules / Q000502:physiology*; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D008941:Spindle Apparatus / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D020730:Guanine Nucleotide Dissociation Inhibitors; C104644:Khc-73 protein, Drosophila; D009419:Nerve Tissue Proteins; C405164:Pins protein, Drosophila; D025521:Tumor Suppressor Proteins; C070350:dlg1 protein, Drosophila; D016547:Kinesins; D019206:GTP-Binding Protein alpha Subunits, Gi-Go