Siegrist Sarah E, Doe Chris Q
Institutes of Neuroscience and Molecular Biology, Howard Hughes Medical Institute, University of Oregon, Eugene, Oregon 97403, USA.
Cell. 2005 Dec 29;123(7):1323-35. doi: 10.1016/j.cell.2005.09.043.
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.
皮层极性调节细胞分裂、迁移和分化。微管在酵母中诱导皮层极性，但在后生动物中已知的例子很少。我们发现星状微管、驱动蛋白Khc-73和盘状大蛋白（Dlg）在果蝇神经母细胞中诱导Pins/Gαi的皮层极化；这个皮层区域对于产生纺锤体不对称、子细胞大小不对称和不同的姐妹细胞命运具有功能。Khc-73定位于星状微管的正端，并且Dlg/Khc-73和Dlg/Pins能进行共免疫沉淀，这表明微管通过Dlg/Khc-73相互作用诱导Pins/Gαi的皮层极性。微管/Khc-73/Dlg途径与特征明确的Inscuteable/Par途径平行发挥作用，但每条途径都提供独特的空间和时间信息：Inscuteable/Par途径在前期启动，以协调神经母细胞皮层极性与中枢神经系统组织极性，而微管/Khc-73/Dlg途径在中期发挥作用，以协调神经母细胞皮层极性与有丝分裂纺锤体轴。这些结果确定了微管在使神经母细胞皮层极化中的作用，这是通过不对称细胞分裂产生细胞多样性的一个基本步骤。
