Moreira Sofia, Morais-de-Sá Eurico
a IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto , Porto , Portugal.
b I3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto , Porto , Portugal.
Bioarchitecture. 2016;6(2):29-38. doi: 10.1080/19490992.2016.1149290.
Intracellular asymmetries, often termed cell polarity, determine how cells organize and divide to ultimately control cell fate and shape animal tissues. The tumor suppressor Lethal giant larvae (Lgl) functions at the core of the evolutionarily conserved cell polarity machinery that controls apico-basal polarization. This function relies on its restricted basolateral localization via phosphorylation by aPKC. Here, we summarize the spatial and temporal control of Lgl during the cell cycle, highlighting two ideas that emerged from our recent findings: 1) Aurora A directly phosphorylates Lgl during symmetric division to couple reorganization of epithelial polarity with the cell cycle; 2) Phosphorylation of Lgl within three conserved serines controls its localization and function in a site-specific manner. Considering the importance of phosphorylation to regulate the concentration of Lgl at the plasma membrane, we will further discuss how it may work as an on-off switch for the interaction with cortical binding partners, with implications on epithelial polarization and spindle orientation.
细胞内的不对称性，通常称为细胞极性，决定了细胞如何组织和分裂，最终控制细胞命运并塑造动物组织。肿瘤抑制因子致死性巨幼虫（Lgl）在控制顶-基极化的进化保守细胞极性机制的核心发挥作用。该功能依赖于通过非典型蛋白激酶C（aPKC）磷酸化使其定位于基底外侧。在这里，我们总结了细胞周期中Lgl的时空控制，强调了我们最近的发现中出现的两个观点：1）在对称分裂过程中，极光激酶A（Aurora A）直接磷酸化Lgl，使上皮极性的重组与细胞周期耦合；2）Lgl三个保守丝氨酸位点的磷酸化以位点特异性方式控制其定位和功能。考虑到磷酸化对调节Lgl在质膜上浓度的重要性，我们将进一步讨论它如何作为与皮质结合伴侣相互作用的开关，这对上皮极化和纺锤体定向具有重要意义。
