Yu J, Manabe M, Sun T T
Department of Dermatology, New York University Medical School, New York 10016.
Epithelial Cell Biol. 1992 Jan;1(1):4-12.
Although bladder cancers account for almost 5% of all human cancer deaths, little is known about the biochemistry of urothelial differentiation. We have recently identified three major protein subunits ('uroplakins') of asymmetric unit membranes (AUM), which form rigid-looking plaques covering up to 70% of the apical surface of urothelial superficial (umbrella) cells. The ordinary-looking plasma membranes that interconnect these plaques are believed to be functionally specialized, serving as flexible but durable 'hinges'. Whether these hinge membranes are biochemically unique is unknown. Using a new monoclonal antibody (AE32) we have identified an 85-100 kDa glycoprotein (UGP85) which appears to be urothelium-specific. In both normal urothelium and cultured urothelial colonies this cell surface protein is associated mainly with superficial cells, suggesting that its expression is differentiation dependent. Results from in vitro translation experiments indicated that this glycoprotein contains a core polypeptide of about 55 kDa. Using immunogold localization techniques, we showed that in cultured urothelial colonies--which are known to lack mature AUM plaques--UGP85 is distributed relatively uniformly on the apical surface of some differentiated cells. However, in superficial cells of normal urothelium UGP85 is mainly associated with the hinge areas. These results raise the possibility that UGP85 is a plasma membrane component which can be excluded, to varying extents, from the plaque region as 12 nm protein particles are assembled into a tightly packed paracrystalline AUM structure. The identification of UGP85 provides the first evidence that the hinge areas interconnecting the urothelial plaques are biochemically distinguishable from the plasma membranes of the relatively undifferentiated urothelial cells of the lower cell layers.(ABSTRACT TRUNCATED AT 250 WORDS)
尽管膀胱癌占人类癌症死亡总数的近5%，但关于尿路上皮分化的生物化学却知之甚少。我们最近鉴定出不对称单位膜（AUM）的三个主要蛋白质亚基（“uroplakins”），它们形成外观坚硬的斑块，覆盖尿路上皮表层（伞状）细胞高达70%的顶端表面。连接这些斑块的看似普通的质膜被认为在功能上具有特殊性，充当灵活但耐用的“铰链”。这些铰链膜在生物化学上是否独特尚不清楚。使用一种新的单克隆抗体（AE32），我们鉴定出一种85 - 100 kDa的糖蛋白（UGP85），它似乎是尿路上皮特异性的。在正常尿路上皮和培养的尿路上皮菌落中，这种细胞表面蛋白主要与表层细胞相关，表明其表达依赖于分化。体外翻译实验结果表明，这种糖蛋白含有一个约55 kDa的核心多肽。使用免疫金定位技术，我们发现，在已知缺乏成熟AUM斑块的培养尿路上皮菌落中，UGP85相对均匀地分布在一些分化细胞的顶端表面。然而，在正常尿路上皮的表层细胞中，UGP85主要与铰链区域相关。这些结果增加了一种可能性，即UGP85是一种质膜成分，随着12 nm蛋白质颗粒组装成紧密堆积的准晶体AUM结构，它可以在不同程度上被排除在斑块区域之外。UGP85的鉴定提供了首个证据，表明连接尿路上皮斑块的铰链区域在生物化学上与下层相对未分化的尿路上皮细胞质膜不同。（摘要截短于250字）
