Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai, PR China.
Mol Cell. 2011 Aug 5;43(3):418-31. doi: 10.1016/j.molcel.2011.07.011.
Asymmetric cell division requires the establishment of cortical cell polarity and the orientation of the mitotic spindle along the axis of cell polarity. Evidence from invertebrates demonstrates that the Par3/Par6/aPKC and NuMA/LGN/Gαi complexes, which are thought to be physically linked by the adaptor protein mInscuteable (mInsc), play indispensable roles in this process. However, the molecular basis for the binding of LGN to NuMA and mInsc is poorly understood. The high-resolution structures of the LGN/NuMA and LGN/mInsc complexes presented here provide mechanistic insights into the distinct and highly specific interactions of the LGN TPRs with mInsc and NuMA. Structural comparisons, together with biochemical and cell biology studies, demonstrate that the interactions of NuMA and mInsc with LGN are mutually exclusive, with mInsc binding preferentially. Our results suggest that the Par3/mInsc/LGN and NuMA/LGN/Gαi complexes play sequential and partially overlapping roles in asymmetric cell division.
不对称细胞分裂需要建立皮质细胞极性，并沿着细胞极性的轴定向有丝分裂纺锤体。来自无脊椎动物的证据表明，Par3/Par6/aPKC 和 NuMA/LGN/Gαi 复合物，被认为通过衔接蛋白 mInscuteable (mInsc) 物理连接，在这个过程中发挥不可或缺的作用。然而，LGN 与 NuMA 和 mInsc 结合的分子基础理解得还很差。这里呈现的 LGN/NuMA 和 LGN/mInsc 复合物的高分辨率结构，为 LGN TPR 与 mInsc 和 NuMA 的独特且高度特异性相互作用提供了机制见解。结构比较，以及生化和细胞生物学研究，表明 NuMA 和 mInsc 与 LGN 的相互作用是相互排斥的，mInsc 优先结合。我们的结果表明，Par3/mInsc/LGN 和 NuMA/LGN/Gαi 复合物在不对称细胞分裂中发挥连续的和部分重叠的作用。
