Rolls Melissa M, Albertson Roger, Shih Hsin-Pei, Lee Cheng-Yu, Doe Chris Q
Institutes of Neuroscience and Molecular Biology, Howard Hughes Medical Institute, 1254 University of Oregon, Eugene, OR 97403, USA.
J Cell Biol. 2003 Dec 8;163(5):1089-98. doi: 10.1083/jcb.200306079. Epub 2003 Dec 1.
Cell polarity is essential for generating cell diversity and for the proper function of most differentiated cell types. In many organisms, cell polarity is regulated by the atypical protein kinase C (aPKC), Bazooka (Baz/Par3), and Par6 proteins. Here, we show that Drosophila aPKC zygotic null mutants survive to mid-larval stages, where they exhibit defects in neuroblast and epithelial cell polarity. Mutant neuroblasts lack apical localization of Par6 and Lgl, and fail to exclude Miranda from the apical cortex; yet, they show normal apical crescents of Baz/Par3, Pins, Inscuteable, and Discs large and normal spindle orientation. Mutant imaginal disc epithelia have defects in apical/basal cell polarity and tissue morphology. In addition, we show that aPKC mutants show reduced cell proliferation in both neuroblasts and epithelia, the opposite of the lethal giant larvae (lgl) tumor suppressor phenotype, and that reduced aPKC levels strongly suppress most lgl cell polarity and overproliferation phenotypes.
细胞极性对于产生细胞多样性以及大多数分化细胞类型的正常功能至关重要。在许多生物体中，细胞极性由非典型蛋白激酶C（aPKC）、巴祖卡蛋白（Baz/Par3）和Par6蛋白调控。在此，我们表明果蝇aPKC合子型无效突变体能够存活至幼虫中期阶段，在此阶段它们在神经母细胞和上皮细胞极性方面表现出缺陷。突变的神经母细胞缺乏Par6和Lgl的顶端定位，并且无法将米兰达蛋白排除在顶端皮质之外；然而，它们显示出Baz/Par3、Pins、Inscuteable和盘状大蛋白的正常顶端新月形以及正常的纺锤体取向。突变的成虫盘上皮细胞在顶端/基底细胞极性和组织形态方面存在缺陷。此外，我们表明aPKC突变体在神经母细胞和上皮细胞中均表现出细胞增殖减少，这与致死性巨幼虫（lgl）肿瘤抑制表型相反，并且aPKC水平降低强烈抑制大多数lgl细胞极性和过度增殖表型。
