Carvalho Cátia A, Moreira Sofia, Ventura Guilherme, Sunkel Cláudio E, Morais-de-Sá Eurico
Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal; Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
Curr Biol. 2015 Jan 5;25(1):53-60. doi: 10.1016/j.cub.2014.10.053. Epub 2014 Dec 4.
Mitotic spindle orientation is essential to control cell-fate specification and epithelial architecture. The tumor suppressor Lgl localizes to the basolateral cortex of epithelial cells, where it acts together with Dlg and Scrib to organize apicobasal polarity. Dlg and Scrib also control planar spindle orientation, but how the organization of polarity complexes is adjusted to control symmetric division is largely unknown. Here, we show that the Dlg complex is remodeled during Drosophila follicular epithelium cell division, when Lgl is released to the cytoplasm. Lgl redistribution during epithelial mitosis is reminiscent of asymmetric cell division, where it is proposed that Aurora A promotes aPKC activation to control the localization of Lgl and cell-fate determinants. We show that Aurora A controls Lgl localization directly, triggering its cortical release at early prophase in both epithelial and S2 cells. This relies on double phosphorylation within the putative aPKC phosphorylation site, which is required and sufficient for Lgl cortical release during mitosis and can be achieved by a combination of aPKC and Aurora A activities. Cortical retention of Lgl disrupts planar spindle orientation, but only when Lgl mutants that can bind Dlg are expressed. Hence, our work reveals that Lgl mitotic cortical release is not specifically linked to the asymmetric segregation of fate determinants, and we propose that Aurora A activation breaks the Dlg/Lgl interaction to allow planar spindle orientation during symmetric division via the Pins (LGN)/Dlg pathway.
有丝分裂纺锤体的定向对于控制细胞命运特化和上皮结构至关重要。肿瘤抑制因子Lgl定位于上皮细胞的基底外侧皮质，在那里它与Dlg和Scrib共同作用以组织顶-基极性。Dlg和Scrib也控制平面纺锤体定向，但极性复合物的组织如何被调节以控制对称分裂在很大程度上尚不清楚。在这里，我们表明Dlg复合物在果蝇卵泡上皮细胞分裂过程中发生重塑，此时Lgl释放到细胞质中。上皮细胞有丝分裂期间Lgl的重新分布让人联想到不对称细胞分裂，在不对称细胞分裂中，有人提出极光激酶A促进非典型蛋白激酶C（aPKC）的激活以控制Lgl和细胞命运决定因子的定位。我们表明极光激酶A直接控制Lgl的定位，在上皮细胞和S2细胞的前期早期触发其从皮质释放。这依赖于假定的aPKC磷酸化位点内的双重磷酸化，这在有丝分裂期间对于Lgl从皮质释放是必需且充分的，并且可以通过aPKC和极光激酶A的活性组合来实现。Lgl在皮质的保留会破坏平面纺锤体定向，但仅当表达能够结合Dlg的Lgl突变体时才会如此。因此，我们的工作表明Lgl有丝分裂时从皮质释放并非与命运决定因子的不对称分离特别相关，并且我们提出极光激酶A的激活会破坏Dlg/Lgl相互作用，从而通过Pins（LGN）/Dlg途径在对称分裂期间允许平面纺锤体定向。
