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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Inscuteable and NuMA proteins bind competitively to Leu-Gly-Asn repeat-enriched protein (LGN) during asymmetric cell divisions
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Inscuteable and NuMA proteins bind competitively to Leu-Gly-Asn repeat-enriched protein (LGN) during asymmetric cell divisions

机译：不对称和NuMA蛋白在不对称细胞分裂过程中与Leu-Gly-Asn重复富集蛋白（LGN）竞争性结合

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摘要

Coupling of spindle orientation to cellular polarity is a prerequisite for epithelial asymmetric cell divisions. The current view posits that the adaptor Inscuteable (Insc) bridges between Par3 and the spindle tethering machinery assembled on NuMA: LGN: Gαi~(GDP), thus triggering apico-basal spindle orientation. The crystal structure of the Drosophila ortholog of LGN (known as Pins) in complex with Insc reveals a modular interface contributed by evolutionary conserved residues. The structure also identifies a positively charged patch of LGN binding to an invariant EPE-motif present on both Insc and NuMA. In vitro competition assays indicate that Insc competes with NuMA for LGN binding, displaying a higher affinity, and that it is capable of opening the LGN conformational switch. The finding that Insc and NuMA are mutually exclusive interactors of LGN challenges the established model of force generators assembly, which we revise on the basis of the newly discovered biochemical properties of the intervening components.
机译：纺锤方向与细胞极性的耦合是上皮不对称细胞分裂的前提。当前观点认为，适配器Inscuteable（Insc）在Par3和NuMA上组装的主轴系绳机之间架起了桥梁：LGN：Gαi〜（GDP），从而触发了土基-基础主轴定向。与Insc结合的LGN果蝇直系同源物（称为Pins）的晶体结构揭示了由保守保守残基贡献的模块界面。该结构还鉴定了与Insc和NuMA上均存在的不变EPE基序结合的LGN带正电荷的补丁。体外竞争分析表明，Insc与NuMA竞争LGN结合，表现出更高的亲和力，并且能够打开LGN构象开关。 Insc和NuMA是LGN相互排斥的相互作用者的发现，对建立的力发生器装配模型提出了挑战，我们将根据新发现的中间组件的生化特性对其进行修改。

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    Simone Culurgioni; Andrea Alfieri; Valentina Pendolino; Federica Laddomada; Marina Mapelli;

  • 作者单位

    Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20139 Milan, Italy;

    Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20139 Milan, Italy;

    Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20139 Milan, Italy;

    Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20139 Milan, Italy;

    Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20139 Milan, Italy;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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