Tabuse Y, Izumi Y, Piano F, Kemphues K J, Miwa J, Ohno S
Fundamental Research Laboratories, NEC Corporation, Tsukuba, Ibaraki 305, Japan.
Development. 1998 Sep;125(18):3607-14. doi: 10.1242/dev.125.18.3607.
Asymmetric cell divisions, critically important to specify cell types in the development of multicellular organisms, require polarized distribution of cytoplasmic components and the proper alignment of the mitotic apparatus. In Caenorhabditis elegans, the maternally expressed protein, PAR-3, is localized to one pole of asymmetrically dividing blastomeres and is required for these asymmetric divisions. In this paper, we report that an atypical protein kinase C (PKC-3) is essential for proper asymmetric cell divisions and co-localizes with PAR-3. Embryos depleted of PKC-3 by RNA interference die showing Par-like phenotypes including defects in early asymmetric divisions and mislocalized germline-specific granules (P granules). The defective phenotypes of PKC-3-depleted embryos are similar to those exhibited by mutants for par-3 and another par gene, par-6. Direct interaction of PKC-3 with PAR-3 is shown by in vitro binding analysis. This result is reinforced by the observation that PKC-3 and PAR-3 co-localize in vivo. Furthermore, PKC-3 and PAR-3 show mutual dependence on each other and on three of the other par genes for their localization. We conclude that PKC-3 plays an indispensable role in establishing embryonic polarity through interaction with PAR-3.
不对称细胞分裂对于多细胞生物体发育过程中细胞类型的确定至关重要,它需要细胞质成分的极化分布以及有丝分裂装置的正确排列。在秀丽隐杆线虫中,母源表达的蛋白质PAR-3定位于不对称分裂的卵裂球的一极,并且是这些不对称分裂所必需的。在本文中,我们报道一种非典型蛋白激酶C(PKC-3)对于正确的不对称细胞分裂至关重要,并且与PAR-3共定位。通过RNA干扰使PKC-3缺失的胚胎死亡,表现出类似Par的表型,包括早期不对称分裂缺陷和种系特异性颗粒(P颗粒)定位错误。PKC-3缺失胚胎的缺陷表型与par-3和另一个par基因par-6的突变体所表现出的表型相似。体外结合分析表明PKC-3与PAR-3直接相互作用。PKC-3和PAR-3在体内共定位的观察结果进一步证实了这一结果。此外,PKC-3和PAR-3在定位上相互依赖,并且依赖于其他三个par基因。我们得出结论,PKC-3通过与PAR-3相互作用在建立胚胎极性中发挥不可或缺的作用。