Cox D N, Seyfried S A, Jan L Y, Jan Y N
Howard Hughes Medical Institute, Department of Physiology, University of California, 533 Parnassus Avenue, Room U426, Box 0725, San Francisco, CA 94143-0725, USA.
Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14475-80. doi: 10.1073/pnas.261565198.
The par genes, identified by their role in the establishment of anterior-posterior polarity in the Caenorhabditis elegans zygote, subsequently have been shown to regulate cellular polarity in diverse cell types by means of an evolutionarily conserved protein complex including PAR-3, PAR-6, and atypical protein kinase C (aPKC). The Drosophila homologs of par-1, par-3 (bazooka, baz), par-6 (DmPar-6), and pkc-3 (Drosophila aPKC, DaPKC) each are known to play conserved roles in the generation of cell polarity in the germ line as well as in epithelial and neural precursor cells within the embryo. In light of this functional conservation, we examined the potential role of baz and DaPKC in the regulation of oocyte polarity. Our analyses reveal germ-line autonomous roles for baz and DaPKC in the establishment of initial anterior-posterior polarity within germ-line cysts and maintenance of oocyte cell fate. Germ-line clonal analyses indicate both proteins are essential for two key aspects of oocyte determination: the posterior translocation of oocyte specification factors and the posterior establishment of the microtubule organizing center within the presumptive oocyte. We demonstrate BAZ and DaPKC colocalize to belt-like structures between germarial cyst cells. However, in contrast to their regulatory relationship in the Drosophila and C. elegans embryos, these proteins are not mutually dependent for their germ-line localization, nor is either protein specifically required for PAR-1 localization to the fusome. Therefore, whereas BAZ, DaPKC, and PAR-1 are functionally conserved in establishing oocyte polarity, the regulatory relationships among these genes are not well conserved, indicating these molecules function differently in different cellular contexts.
par基因最初是因其在秀丽隐杆线虫受精卵前后极性建立过程中的作用而被鉴定出来的,随后研究表明,它们通过一种进化上保守的蛋白复合物(包括PAR-3、PAR-6和非典型蛋白激酶C(aPKC))来调节多种细胞类型中的细胞极性。已知par-1、par-3(bazooka,baz)、par-6(DmPar-6)和pkc-3(果蝇aPKC,DaPKC)的果蝇同源物在生殖系以及胚胎内的上皮和神经前体细胞的细胞极性产生中发挥保守作用。鉴于这种功能上的保守性,我们研究了baz和DaPKC在卵母细胞极性调节中的潜在作用。我们的分析揭示了baz和DaPKC在生殖系囊肿内初始前后极性建立以及卵母细胞命运维持中的生殖系自主作用。生殖系克隆分析表明,这两种蛋白对于卵母细胞决定的两个关键方面至关重要:卵母细胞特异性因子的后位转运以及推定卵母细胞内微管组织中心的后位建立。我们证明BAZ和DaPKC共定位于生殖细胞囊肿细胞之间的带状结构。然而,与它们在果蝇和秀丽隐杆线虫胚胎中的调控关系不同,这些蛋白在生殖系中的定位并不相互依赖,PAR-1定位于纺锤体也不特别需要这两种蛋白中的任何一种。因此,虽然BAZ、DaPKC和PAR-1在建立卵母细胞极性方面功能保守,但这些基因之间的调控关系并不保守,这表明这些分子在不同的细胞环境中发挥不同的作用。