LGN regulates mitotic spindle orientation during epithelial morphogenesis.
LGN regulates mitotic spindle orientation during epithelial morphogenesis.
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DOI：
10.1083/jcb.200910021
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发表时间：
2010-04-19
期刊：
影响因子：
--
通讯作者：
Du Q
中科院分区：
文献类型：
--
作者：
Zheng Z;Zhu H;Wan Q;Liu J;Xiao Z;Siderovski DP;Du Q
破坏LGN在侧膜结构域的功能，会使囊肿形成MDCK细胞中的细胞分裂轴移位。协调的细胞极化和有丝分裂纺锤体的方向被认为是重要的上皮形态发生。纺锤体方向是否确实与上皮形态发生有关，以及它是如何在分子水平上被控制的仍然是未知的。在这里，我们表明NuMA和Gα结合蛋白LGN是在MDCK细胞的囊形成过程中指导纺锤体方向所必需的。LGN定位于外侧细胞皮层，并被排除在分裂细胞的顶细胞皮层之外。耗尽LGN、阻止其皮质定位或破坏其与内源性NuMA或Gα蛋白的相互作用均导致纺锤体定向错误和异常囊形成。此外，内源性LGN与顶膜的人为错误定位导致纺锤体轴旋转近90°，并导致依赖于细胞分裂的严重囊形成缺陷。在有丝分裂过程中，LGN的正常顶端排斥似乎是由非典型PKC介导的。因此，细胞极化介导的空间限制的纺锤体方向决定因素是至关重要的上皮形态发生。
Disrupting LGN’s function at lateral membrane domains displaces the axis of cell division in cyst-forming MDCK cells. Coordinated cell polarization and mitotic spindle orientation are thought to be important for epithelial morphogenesis. Whether spindle orientation is indeed linked to epithelial morphogenesis and how it is controlled at the molecular level is still unknown. Here, we show that the NuMA- and Gα-binding protein LGN is required for directing spindle orientation during cystogenesis of MDCK cells. LGN localizes to the lateral cell cortex, and is excluded from the apical cell cortex of dividing cells. Depleting LGN, preventing its cortical localization, or disrupting its interaction with endogenous NuMA or Gα proteins all lead to spindle misorientation and abnormal cystogenesis. Moreover, artificial mistargeting of endogenous LGN to the apical membrane results in a near 90° rotation of the spindle axis and profound cystogenesis defects that are dependent on cell division. The normal apical exclusion of LGN during mitosis appears to be mediated by atypical PKC. Thus, cell polarization–mediated spatial restriction of spindle orientation determinants is critical for epithelial morphogenesis.
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