Insc:LGN tetramers promote asymmetric divisions of mammary stem cells.
Insc:LGN tetramers promote asymmetric divisions of mammary stem cells.
复制标题
DOI：
10.1038/s41467-018-03343-4
复制
发表时间：
2018-03-09
影响因子：
16.6
通讯作者：
Mapelli M
中科院分区：
文献类型：
--
作者：
Culurgioni S;Mari S;Bonetti P;Gallini S;Bonetto G;Brennich M;Round A;Nicassio F;Mapelli M
不对称细胞分裂平衡干细胞增殖和分化，以维持组织形态发生和稳态。在不对称分裂，命运的决定因素和生态位接触之间的女儿不平等隔离，但很少有人知道这是如何实现的机械。在果蝇神经母细胞和小鼠乳腺干细胞中，纺锤体定向蛋白LGN与干细胞适配器Insuteable的关联与不对称性有关。在这里，我们报告的晶体结构的果蝇LGN复杂的不对称结构域的不可见，揭示了一个四聚体排列的相互交织的分子。我们表明，Insc：LGN四聚体构成Par 3-Insc-LGN-GαiGDP复合物的稳定核心，其不能被NuMA解离。在乳腺干细胞中，与LGN：GαiGDP结合的Insc的不对称结构域足以驱动不对称命运，并逆转由p53缺失诱导的异常对称分裂。我们提出了一个新的作用，独立的微管马达，以促进不对称的命运规范的LGN的INSC结合池。在不对称分裂过程中，子细胞之间的命运决定子和生态位接触不均等地分离，但其机制尚不清楚。在本文中，作者表明，Insc：LGN四聚体促进Par 3-Insc-LGN-GαiGDP复合物的组装和不对称命运特化，与微管马达无关。
Asymmetric cell divisions balance stem cell proliferation and differentiation to sustain tissue morphogenesis and homeostasis. During asymmetric divisions, fate determinants and niche contacts segregate unequally between daughters, but little is known on how this is achieved mechanistically. In Drosophila neuroblasts and murine mammary stem cells, the association of the spindle orientation protein LGN with the stem cell adaptor Inscuteable has been connected to asymmetry. Here we report the crystal structure of Drosophila LGN in complex with the asymmetric domain of Inscuteable, which reveals a tetrameric arrangement of intertwined molecules. We show that Insc:LGN tetramers constitute stable cores of Par3–Insc-LGN-GαiGDP complexes, which cannot be dissociated by NuMA. In mammary stem cells, the asymmetric domain of Insc bound to LGN:GαiGDP suffices to drive asymmetric fate, and reverts aberrant symmetric divisions induced by p53 loss. We suggest a novel role for the Insc-bound pool of LGN acting independently of microtubule motors to promote asymmetric fate specification. During asymmetric divisions fate determinants and niche contacts segregate unequally between daughter cells, but the mechanism is unclear. Here the authors show that Insc:LGN tetramers promote assembly of Par3-Insc-LGN-GαiGDP complexes and asymmetric fate specification independently of microtubule motors.
登录
查看更多内容
影响因子：
64.8
作者：
Colaluca, Ivan N.;Tosoni, Daniela;Di Fiore, Pier Paolo
通讯作者：
Di Fiore, Pier Paolo
影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
影响因子：
64.8
作者：
Chang, Leifu;Zhang, Ziguo;Yang, Jing;McLaughlin, Stephen H.;Barford, David
通讯作者：
Barford, David
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
3
作者：
Pettersen, EF;Goddard, TD;Ferrin, TE
通讯作者：
Ferrin, TE