Institut Jacques Monod, CNRS-Universite Paris Diderot, Bât. Buffon -15 rue Hélène Brion, 75205 Paris cedex 13, France.
Development. 2010 Mar;137(5):815-24. doi: 10.1242/dev.045013.
Most cell types in an organism show some degree of polarization, which relies on a surprisingly limited number of proteins. The underlying molecular mechanisms depend, however, on the cellular context. Mutual inhibitions between members of the Par genes are proposed to be sufficient to polarize the C. elegans one-cell zygote and the Drosophila oocyte during mid-oogenesis. By contrast, the Par genes interact with cellular junctions and associated complexes to polarize epithelial cells. The Par genes are also required at an early step of Drosophila oogenesis for the maintenance of the oocyte fate and its early polarization. Here we show that the Par genes are not sufficient to polarize the oocyte early and that the activity of the tumor-suppressor gene lethal giant larvae (lgl) is required for the posterior translocation of oocyte-specific proteins, including germline determinants. We also found that Lgl localizes asymmetrically within the oocyte and is excluded from the posterior pole. We further demonstrate that phosphorylation of Par-1, Par-3 (Bazooka) and Lgl is crucial to regulate their activity and localization in vivo and describe, for the first time, adherens junctions located around the ring canals, which link the oocyte to the other cells of the germline cyst. However, null mutations in the DE-cadherin gene, which encodes the main component of the zonula adherens, do not affect the early polarization of the oocyte. We conclude that, despite sharing many similarities with other model systems at the genetic and cellular levels, the polarization of the early oocyte relies on a specific subset of polarity proteins.
生物体内的大多数细胞类型都表现出一定程度的极化，而这种极化依赖于数量惊人的有限的蛋白质。然而，潜在的分子机制取决于细胞环境。在秀丽隐杆线虫的单细胞合子和果蝇的卵母细胞中期发生过程中，Par 基因成员之间的相互抑制被认为足以使它们发生极化。相比之下，Par 基因通过与细胞连接和相关复合物相互作用来使上皮细胞极化。Par 基因也在果蝇卵母细胞发生的早期阶段对于维持卵母细胞命运及其早期极化是必需的。在这里，我们表明 Par 基因不足以使卵母细胞早期极化，并且肿瘤抑制基因 lethal giant larvae (lgl) 的活性对于卵母细胞特异性蛋白（包括生殖细胞决定因子）的后向易位是必需的。我们还发现 Lgl 在卵母细胞内不对称定位，并被排除在后极。我们进一步证明，Par-1、Par-3（Bazooka）和 Lgl 的磷酸化对于调节它们在体内的活性和定位至关重要，并首次描述了位于环管周围的黏附连接，环管将卵母细胞与生殖细胞囊的其他细胞连接起来。然而，缺失 DE-cadherin 基因（该基因编码黏附连接的主要成分）不会影响卵母细胞的早期极化。我们的结论是，尽管在遗传和细胞水平上与其他模型系统有许多相似之处，但早期卵母细胞的极化依赖于一组特定的极性蛋白。
