Betschinger Jörg, Mechtler Karl, Knoblich Juergen A
Research Institute of Molecular Pathology, Dr Bohr Gasse 7, 1030 Vienna, Austria.
Nature. 2003 Mar 20;422(6929):326-30. doi: 10.1038/nature01486. Epub 2003 Mar 9.
To generate different cell types, some cells can segregate protein determinants into one of their two daughter cells during mitosis. In Drosophila neuroblasts, the Par protein complex localizes apically and directs localization of the cell fate determinants Prospero and Numb and the adaptor proteins Miranda and Pon to the basal cell cortex, to ensure their segregation into the basal daughter cell. The Par protein complex has a conserved function in establishing cell polarity but how it directs proteins to the opposite side is unknown. We show here that a principal function of this complex is to phosphorylate the cytoskeletal protein Lethal (2) giant larvae (Lgl; also known as L(2)gl). Phosphorylation by Drosophila atypical protein kinase C (aPKC), a member of the Par protein complex, releases Lgl from its association with membranes and the actin cytoskeleton. Genetic and biochemical experiments show that Lgl phosphorylation prevents the localization of cell fate determinants to the apical cell cortex. Lgl promotes cortical localization of Miranda, and we propose that phosphorylation of Lgl by aPKC at the apical neuroblast cortex restricts Lgl activity and Miranda localization to the opposite, basal side of the cell.
为了生成不同的细胞类型，一些细胞在有丝分裂期间可将蛋白质决定因子分离到其两个子细胞之一中。在果蝇神经母细胞中，Par蛋白复合物定位于顶端，并将细胞命运决定因子Prospero和Numb以及衔接蛋白Miranda和Pon引导至基底细胞皮层，以确保它们分离到基底子细胞中。Par蛋白复合物在建立细胞极性方面具有保守功能，但它如何将蛋白质引导至细胞相对侧尚不清楚。我们在此表明，该复合物的主要功能是磷酸化细胞骨架蛋白致死（2）大幼虫（Lgl；也称为L(2)gl）。果蝇非典型蛋白激酶C（aPKC）是Par蛋白复合物的成员之一，其磷酸化作用使Lgl与其与膜和肌动蛋白细胞骨架的结合解离。遗传和生化实验表明，Lgl磷酸化可阻止细胞命运决定因子定位于顶端细胞皮层。Lgl促进Miranda的皮层定位，并且我们提出，在顶端神经母细胞皮层处aPKC对Lgl的磷酸化作用将Lgl活性和Miranda定位限制在细胞相对的基底侧。
