Sato Ken-Ichi
Laboratory of Cell and Developmental Biology, Department of Biotechnology, Faculty of Engineering, Kyoto Sangyo University, Kamigamo-Motoyama, Kyoto 603-8555, Japan.
Open Biochem J. 2008;2:49-59. doi: 10.2174/1874091X00802010049. Epub 2008 Apr 29.
Membrane microdomains or lipid/membrane rafts are distinct areas on the plasma membranes, where a specific subset of lipids (e.g. cholesterol, sphingolipids) and proteins (e.g. glycosylphosphatidylinositol-anchored proteins, growth factor receptor/kinases) are getting together and functioning for several aspects of cellular functions. Our recent investigation has revealed that fertilization of African clawed frog, Xenopus laevis, requires cholesterol-dependent nature of egg membrane microdomains. Moreover, fertilization of Xenopus eggs involves proteolytic cleavage of the extracellular part and subsequent phosphorylation of a cytoplasmic tyrosine residue of uroplakin III, an egg membrane microdomain-associated protein. Protease activity toward uroplakin III seems to be derived from fertilizing sperm, while phosphorylation of uroplakin III seems to be catalyzed by the egg tyrosine kinase Src, whose activation is required for cytoplasmic rearrangement of fertilized eggs; so-called 'egg activation'. Therefore, it is assumed that uroplakin III serves an integral part of signal transduction in fertilization of Xenopus. Our more recent study on human cancer cells has revealed that a similar but distinct scheme of signal transduction operates in anti-apoptotic growth of cells. Namely, in human bladder carcinoma cells, cooperation of uroplakin III and Src, both of which localize to the membrane microdomains, allows cells to escape from apoptotic cell death and proliferate under culture conditions deprived of serum. In this review, I briefly introduce about biology of fertilization and cancer, and then present and discuss our experimental data on general importance and specific features of membrane microdomains in Xenopus fertilization and anti-apoptosis in human bladder carcinoma cells.
膜微区或脂筏/膜筏是质膜上的独特区域，特定的脂质亚群（如胆固醇、鞘脂）和蛋白质（如糖基磷脂酰肌醇锚定蛋白、生长因子受体/激酶）在此聚集并参与细胞功能的多个方面。我们最近的研究表明，非洲爪蟾（非洲爪蟾）的受精过程需要卵膜微区具有胆固醇依赖性。此外，非洲爪蟾卵的受精涉及胞外部分的蛋白水解切割以及尿路上皮蛋白III（一种卵膜微区相关蛋白）胞质酪氨酸残基的后续磷酸化。针对尿路上皮蛋白III的蛋白酶活性似乎源自受精精子，而尿路上皮蛋白III的磷酸化似乎由卵酪氨酸激酶Src催化，其激活是受精卵胞质重排（即所谓的“卵激活”）所必需的。因此，推测尿路上皮蛋白III在非洲爪蟾受精的信号转导中起不可或缺的作用。我们最近对人类癌细胞的研究表明，一种相似但又不同的信号转导机制在细胞的抗凋亡生长中起作用。也就是说，在人膀胱癌细胞中，定位于膜微区的尿路上皮蛋白III和Src相互协作，使细胞能够在缺乏血清的培养条件下逃避凋亡性细胞死亡并增殖。在这篇综述中，我将简要介绍受精和癌症的生物学知识，然后展示并讨论我们关于膜微区在非洲爪蟾受精和人膀胱癌细胞抗凋亡中的普遍重要性和特定特征的实验数据。
